Head and Neck Cancer, Precancerous Condition
Conditions
Keywords
stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, human papilloma virus infection
Brief summary
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether radiation therapy is more effective with cisplatin or cetuximab in treating oropharyngeal cancer. PURPOSE: This phase III trial is studying radiation therapy with cisplatin or cetuximab to see how well it works in treating patients with oropharyngeal cancer.
Detailed description
OBJECTIVES: Primary * To determine whether substitution of cisplatin with cetuximab will result in comparable 5-year overall survival. Secondary * To monitor and compare progression-free survival for "safety". * To compare patterns of failure (locoregional vs distant). * To compare acute toxicity profiles (and overall toxicity burden). * To compare overall quality of life (QOL) short-term (\< 6 months) and long-term (1 year). * To compare QOL Swallowing Domains short-term and long-term. * To compare clinician-reported versus patient-reported CTCAE toxicity events. * To explore differences in the cost effectiveness of cetuximab as compared to cisplatin. * To explore differences in work status and time to return to work. * To compare patient-reported changes in hearing. * To compare CTCAE v. 4 late toxicity at 1, 2, and 5 years. * To evaluate the effect of tobacco exposure (and other exposures) as measured by standardized computer-assisted self interview (CASI) on overall survival and progression-free survival. * To pilot CASI collection of patient reported outcomes in a cooperative group setting. * To determine whether specific molecular profiles are associated with overall or progression-free survival. * To investigate associations between changes in serum biomarkers or human papilloma virus (HPV)-specific cellular immune responses measured at baseline and three months with overall or progression-free survival. OUTLINE: This is a multicenter study. Patients are stratified according to T stage (T1-2 vs T 3-4), N stage (N0-2a vs N2b-3), Zubrod performance status (0 vs 1), and smoking history (≤ 10 pack-years vs \> 10 pack-years). Patients are randomized to 1 of 2 treatment arms. Patients may complete quality-of-life questionnaires and risk factors for head and neck cancer surveys at baseline, periodically during study, and at follow-up for 1 year. After completion of study therapy, patients are followed up at 1-3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Interventions
BIOLOGICALcetuximab
400 mg/m2 IV 5-7 days before IMRT then 250 mg/m2 IV weekly for 7 weeks
DRUGcisplatin
100 mg/m2 IV on days 1 and 22 of IMRT
RADIATIONIMRT
35 fractions over 6 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 70 Gy.
Sponsors
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
NRG Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
1. Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma and basaloid squamous cell carcinoma) of the oropharynx (tonsil, base of tongue, soft palate, or oropharyngeal walls). 2. Patients must be positive for p16, determined by central review prior to randomization. 3. Patients must have clinically or radiographically evident measurable disease at the primary site or at nodal stations. Tonsillectomy or local excision of the primary without removal of nodal disease is permitted, as is excision removing gross nodal disease but with intact primary site. Limited neck dissections retrieving ≤ 4 nodes are permitted and considered as non-therapeutic nodal excisions. Fine needle aspirations of the neck are insufficient due to limited tissue for retrospective central review. Biopsy specimens from the primary or nodes measuring at least 3-5 mm are required. 4. Clinical stage T1-2, N2a-N3 or T3-4, any N (AJCC, 7th ed.; see Appendix III), including no distant metastases, based upon the following minimum diagnostic workup: * General history and physical examination by a radiation oncologist and medical oncologist within 8 weeks prior to registration; * Examination by an ear, nose, and throat (ENT) or head and neck surgeon, including laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) within 8 weeks prior to registration; * One of the following combinations of imaging is required within 8 weeks prior to registration: 1. A computerized tomography (CT) scan of the neck (with contrast) and a chest CT scan (with or without contrast); 2. or a magnetic resonance imaging (MRI) scan of the neck (with contrast) and a chest CT scan (with or without contrast); 3. or a CT scan of neck (with contrast) and a positron emission tomography (PET)/CT of neck and chest (with or without contrast); 4. or an MRI of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast). Note: A CT scan of neck and/or a PET/CT performed for radiation planning and read by a radiologist may serve as both staging and planning tools. 5. Zubrod Performance Status 0-1 within 2 weeks prior to registration 6. Age ≥ 18; 7. Complete blood count (CBC)/differential obtained within 2 weeks prior to registration on study, with adequate bone marrow function, defined as follows: * Absolute neutrophil count (ANC) \> 1,500 cells/mm3; * Platelets \> 100,000 cells/mm3; * Hemoglobin (Hgb) \> 8.0 g/dl; Note: The use of transfusion or other intervention to achieve Hgb \> 8.0 g/dl is acceptable. 8. Adequate hepatic function, defined as follows: * Bilirubin \< 2 mg/dl within 2 weeks prior to registration; * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 3 x the upper limit of normal within 2 weeks prior to registration; 9. Adequate renal function, defined as follows: • Serum creatinine \< 1.5 mg/dl within 2 weeks prior to registration or creatinine clearance (CCr) ≥ 50 ml/min within 2 weeks prior to registration determined by 24-hour collection or estimated by Cockcroft-Gault formula: CCr male = \[(140 - age) x (wt in kg)\] \[(Serum Cr mg/dl) x (72)\] CCr female = 0.85 x (CCr male) 10. Patients must provide their smoking history (for stratification) via the computer-assisted self interview (CASI) head and neck risk factor survey tool. 11. Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential; 12. Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study and until at least 60 days following the last study treatment. 13. Patients who are human immunodeficiency virus (HIV) positive but have no prior acquired immune deficiency syndrome (AIDS) -defining illness and have CD4 cells of at least 350/mm3 are eligible. Patient HIV status must be known prior to registration. Patients must not be sero-positive for Hepatitis B (Hepatitis B surface antigen positive or anti-hepatitis B core antigen positive) or sero-positive for Hepatitis C (anti-Hepatitis C antibody positive). However, patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B). HIV-positive patients must not have multi-drug resistant HIV infection or other concurrent AIDS-defining conditions. 14. Patient must provide study specific informed consent prior to study entry, including consent for mandatory submission of tissue for required, central p16 review and consent to participate in the computer-assisted self interview (CASI) survey questions regarding smoking history.
Exclusion criteria
1. Cancers considered to be from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal or lip), nasopharynx, hypopharynx, or larynx, even if p16 positive, are excluded. Carcinoma of the neck of unknown primary site origin (even if p16 positive) are excluded from participation. 2. Stage T1-2, N0-1; 3. Distant metastasis or adenopathy below the clavicles; 4. Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. 5. Simultaneous primaries or bilateral tumors; 6. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible); 7. Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable; 8. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields; 9. Severe, active co-morbidity, defined as follows: * 9.1 Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; * 9.2 Transmural myocardial infarction within the last 6 months; * 9.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; * 9.4 Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration; * 9.5 Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol. * 9.6 Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition with immune compromise greater than that noted in Section 3.1.13; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients. 10. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. 11. Prior allergic reaction to cisplatin or cetuximab; 12. Prior cetuximab or other anti-EGFR therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years. | An event for overall survival is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is hazard ratio, which is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years. | An event for progression-free survival is local, regional, or distant disease progression or death due to any cause. Progression-free survival time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is the distribution of progression-free survival times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure. |
| Time to Local-regional Failure | From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years. | Failure for local-regional failure endpoint was defined as local or regional progression, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown \> 20 weeks after the end of radiation therapy, death due to study cancer without documented progression, or death due to unknown causes without documented progression; distant metastasis and death due to other causes were considered competing risks. Local-regional failure time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method. The protocol endpoint is the distribution of local-regional failure times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure. |
| Time to Distant Metastasis | From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years. | Failure for distant metastasis endpoint was defined as distant progression; local-regional failure and death due to any cause were considered competing risks. Distant metastasis time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method. The protocol endpoint is the distribution of distant metastasis times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure. |
| Time to Secondary Primary Cancer | From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years. | Failure for second primary endpoint was defined as reporting of a new primary cancer; death due to any cause was considered a competing risk. Second primary time is defined as time from randomization to the date of second primary or last known follow-up (censored). Rates are estimated by the cumulative incidence method. The protocol endpoint is the distribution of second primary cancer times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure. |
| Distribution of First Progression Events | From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years. | The first event type for progression-free survival is counted for each participant. Possible first progression events are local, regional, or distant progression, any combination of these, or death. The frequency table of these events is also referred to as "Pattern of failure." |
| Percentage of Participants Experiencing Early Death | From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years. | Early death is defined as death due to adverse event or within 30 days of treatment completion. |
| Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: During Treatment | From start of treatment to end of treatment, approximately 6 weeks | Acute adverse events (AE) are defined as occurring within 180 days from the end of treatment. "Treatment-related" means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE |
| Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 1 Month After End of Study Treatment | From start of treatment to approximately 2.5 months (1 month after the end of treatment) | Acute adverse events (AE) are defined as occurring within 180 days from the end of treatment. "Treatment-related" means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE |
| Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 3 Months After the End of Study Treatment | From start of treatment to approximately 4.5 months (3 months after the end of treatment) | Acute adverse events (AE) are defined as occurring within 180 days from the end of treatment. "Treatment-related" means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE |
| Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 6 Months After the End of Study Treatment | From start of treatment to approximately 7.5 months (6 months after the end of treatment) | Acute adverse events (AE) are defined as occurring within 180 days from the end of treatment. "Treatment-related" means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE |
| Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 1 Year After the End of Study Treatment | From start of treatment to approximately 13.5 months (one year after the end of treatment) | Late adverse events (AE) are defined as \> 180 days from end of treatment. "Treatment-related" means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE |
| Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 2 Years After the End of Study Treatment | From 180 days after end of treatment to two years after end of treatment. | Late adverse events (AE) are defined as \> 180 days from end of treatment. "Treatment-related" means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE |
| Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 5 Years After the End of Study Treatment | From start of treatment to approximately 61.5 months (five years after the end of treatment) | Late adverse events (AE) are defined as \> 180 days from end of treatment. "Treatment-related" means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE |
| Percentage of Participants With a Feeding Tube at 1 Year | From randomization to 1 year. | — |
| EORTC QLQ-C30 Global Health Status Score Change From Baseline at End of Treatment | Baseline and end of treatment (6-7 weeks) | The EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30) Global Health Status score measures a cancer patient's perception of their overall health and well-being and ranges from 0 (worst) to 100 (best). A positive change from baseline indicates improvement. |
| EORTC QLQ-C30 Global Health Status Score Change From Baseline at 3 Months From End of Treatment | Baseline and 3 months from end of treatment. Treatment lasts 6-7 weeks. | The EORTC QLQ-C30 Global Health Status score measures a cancer patient's perception of their overall health and well-being and ranges from 0 (worst) to 100 (best). A positive change from baseline indicates improvement. |
| EORTC QLQ-C30 Global Health Status Score Change From Baseline at 6 Months From End of Treatment | Baseline and 6 months from end of treatment. Treatment lasts 6-7 weeks. | The EORTC QLQ-C30 Global Health Status score measures a cancer patient's perception of their overall health and well-being and ranges from 0 (worst) to 100 (best). A positive change from baseline indicates improvement. |
| EORTC QLQ-C30 Global Health Status Score Change From Baseline at 12 Months From End of Treatment | Baseline and 12 months from end of treatment. Treatment lasts 6-7 weeks | The EORTC QLQ-C30 Global Health Status score measures a cancer patient's perception of their overall health and well-being and ranges from 0 (worst) to 100 (best). A positive change from baseline indicates improvement. |
| EORTC QLQ-H&N35 Swallowing Score Change From Baseline at End of Treatment | Baseline and end of treatment (6-7 weeks) | The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Head and Neck Cancer Module (EORTC QLQ-H\&N35) swallowing score measures patient-reported difficulty with swallowing various foods and liquid and ranges from 0 (no swallowing problems) to 100 (maximum swallowing difficulty). A positive change from baseline indicates worsening swallowing function. |
| EORTC QLQ-H&N35 Swallowing Score Change From Baseline at 3 Months From End of Treatment. | Baseline and 3 months from end of treatment. Treatment lasts 6-7 weeks. | The EORTC QLQ-H\&N35 swallowing score measures patient-reported difficulty with swallowing various foods and liquid and ranges from 0 (no swallowing problems) to 100 (maximum swallowing difficulty). A positive change from baseline indicates worsening swallowing function. |
| EORTC QLQ-H&N35 Swallowing Score Change From Baseline at 6 Months From End of Treatment. | Baseline and 6 months from end of treatment. Treatment lasts 6-7 weeks. | The EORTC QLQ-H\&N35 swallowing score measures patient-reported difficulty with swallowing various foods and liquid and ranges from 0 (no swallowing problems) to 100 (maximum swallowing difficulty). A positive change from baseline indicates worsening swallowing function. |
| EORTC QLQ-H&N35 Swallowing Score Change From Baseline at 12 Months From End of Treatment. | Baseline and 12 months from end of treatment. Treatment lasts 6-7 weeks. | The EORTC QLQ-H\&N35 swallowing score measures patient-reported difficulty with swallowing various foods and liquid and ranges from 0 (no swallowing problems) to 100 (maximum swallowing difficulty). A positive change from baseline indicates worsening swallowing function. |
| Number of Participants With Post-baseline Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events for Head and Neck (PRO-CTCAE H&N) Scores >= 3 | End of treatment (approximately 6 weeks after baseline); and 3, 6, and 12 months after end of treatment (approximately 4.5, 7.5, and 13.5 months after baseline). | PRO-CTCAE is a patient-reported outcome (PRO) measurement system developed to evaluate symptomatic toxicity in patients on cancer clinical trials, asking the patient about experience over the last seven days. Scores may reflect worst severity of the symptom (0=None, 1=Mild, 2=Moderate, 3=Severe, and 4=Very severe), frequency of the symptom (0=Never, 1=Rarely, 2=Occasionally, 3=Frequently, 4=Almost constantly), or the symptom's interference with one's "usual or daily activities" (0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, 4=Very much). The symptom row title will indicate "Severity", "Frequency", or "Interference". All scores are compared between arms; statistical analysis results are entered for p-values \< 0.05. |
| EuroQol Five Dimension Scale 3-level Version (EQ-5D-3L) Index Score Change From Baseline | Basline, end of treatment (6-7 weeks), and 3, 6, and 12 months from end of treatment. | The EQ-5D-3L index score measures health-related quality of life using five items (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with three levels of severity (1 = no problems, 2 = moderate problems, 3 = extreme problems). Responses across the five items are combined and transformed into a single utility (index) score. Possible scores range from 0 to 1, with higher scores indicating a better outcome. The change score was calculated as the postbaseline value minus the baseline value. A negative change reflects decline at the postbaseline timepoint and a positive change reflects improvement at the postbaseline timepoint. |
| EuroQol Five Dimension Scale 3-level Version (EQ-5D-3L) Visual Analogue Scale (VAS) Change From Baseline | Basline, end of treatment (6-7 weeks), and 3, 6, and 12 months from end of treatment. | The EQ-5D-3L VAS measures a patient's self-rated current health state using a visual analogue scale measured on a 20-cm scale with 10-point intervals. Scores range from 0 at the bottom of the scale, representing the worst imaginable health state, to 100 at the top of the scale, representing the best imaginable health state. The change score was calculated as the postbaseline value minus the baseline value. A negative change reflects decline at the postbaseline timepoint and a positive change reflects improvement at the postbaseline timepoint. |
| Number of Participants by Work Status Category at Baseline | Baseline | Participants selected all current work status categories that applied. Therefore, category counts are not mutually exclusive and may sum to more than the number of participants analyzed. |
| Number of Participants by Work Status Category at End of Treatment | End of treatment (6-7 weeks) | Participants selected all current work status categories that applied. Therefore, category counts are not mutually exclusive and may sum to more than the number of participants analyzed. |
| Number of Participants by Work Status Category at 3 Months After End of Treatment | Three months after end of treatment (6-7 weeks). | Participants selected all current work status categories that applied. Therefore, category counts are not mutually exclusive and may sum to more than the number of participants analyzed. |
| Number of Participants by Work Status Category at 6 Months After End of Treatment | Six months after end of treatment (6-7 weeks). | Participants selected all current work status categories that applied. Therefore, category counts are not mutually exclusive and may sum to more than the number of participants analyzed. |
| Number of Participants by Work Status Category at 12 Months After End of Treatment | Twelve months after end of treatment (6-7 weeks). | Participants selected all current work status categories that applied. Therefore, category counts are not mutually exclusive and may sum to more than the number of participants analyzed. |
| Percentage of Patients With Normal/Good Dental Health: Pretreatment | Before treatment | This study utilized a dental effects health scale from 0 (normal) to 4 (life-threatening dental condition). The percentage of participants with a value of 0 or 1 is reported: 0 = "Normal: Edentulous, with no gingival disease"; 1 = "Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; \< 5 restorations indicated; no extractions indicated." Ten year data is not yet available. |
| Percentage of Patients With Normal/Good Dental Health: 1 Year After End of Treatment | 1 year after end of treatment (approximately 13.5 months) | This study utilized a dental effects health scale from 0 (normal) to 4 (life-threatening dental condition). The percentage of participants with a value of 0 or 1 is reported: 0 = "Normal: Edentulous, with no gingival disease"; 1 = "Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; \< 5 restorations indicated; no extractions indicated." |
| Percentage of Patients With Normal/Good Dental Health: 2 Years After End of Treatment | 2 years after end of treatment (approximately 25.5 months) | This study utilized a dental effects health scale from 0 (normal) to 4 (life-threatening dental condition). The percentage of participants with a value of 0 or 1 is reported: 0 = "Normal: Edentulous, with no gingival disease"; 1 = "Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; \< 5 restorations indicated; no extractions indicated." |
| Percentage of Patients With Normal/Good Dental Health: 5 Years After End of Treatment | 5 years after end of treatment (approximately 61.5 months) | This study utilized a dental effects health scale from 0 (normal) to 4 (life-threatening dental condition). The percentage of participants with a value of 0 or 1 is reported: 0 = "Normal: Edentulous, with no gingival disease"; 1 = "Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; \< 5 restorations indicated; no extractions indicated." |
| Percentage of Patients With Normal/Good Dental Health: 10 Years After End of Treatment | 10 years after end of treatment (approximately 121.5 months) | This study utilized a dental effects health scale from 0 (normal) to 4 (life-threatening dental condition). The percentage of participants with a value of 0 or 1 is reported: 0 = "Normal: Edentulous, with no gingival disease"; 1 = "Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; \< 5 restorations indicated; no extractions indicated." |
| Number of Participants by HHIA-S Category at Baseline | Baseline | The Hearing Handicap Inventory for Adults Screen Version (HHIA-S) measures a person's perceived hearing handicap. Total score ranges from 0 to 40, with a higher score indicating more severe perceived hearing handicap, categorized as follows: * No handicap: 0-8. * Mild-moderate handicap: 10-24. * Severe handicap: 26-40. |
| Number of Participants by HHIA-S Category at End of Treatment | End of treatment (6-7 weeks) | The Hearing Handicap Inventory for Adults Screen Version (HHIA-S) measures a person's perceived hearing handicap. Total score ranges from 0 to 40, with a higher score indicating more severe perceived hearing handicap, categorized as follows: * No handicap: 0-8. * Mild-moderate handicap: 10-24. * Severe handicap: 26-40. |
| Number of Participants by HHIA-S Category at 3 Months After End of Treatment | 3 months after end of treatment. Treatment lasts 6-7 weeks. | The HHIA-S measures a person's perceived hearing handicap. Total score ranges from 0 to 40, with a higher score indicating more severe perceived hearing handicap, categorized as follows: * No handicap: 0-8. * Mild-moderate handicap: 10-24. * Severe handicap: 26-40. |
| Number of Participants by HHIA-S Category at 6 Months After End of Treatment | 6 months after end of treatment. Treatment lasts 6-7 weeks. | The HHIA-S measures a person's perceived hearing handicap. Total score ranges from 0 to 40, with a higher score indicating more severe perceived hearing handicap, categorized as follows: * No handicap: 0-8. * Mild-moderate handicap: 10-24. * Severe handicap: 26-40. |
| Number of Participants by HHIA-S Category at 12 Months After End of Treatment | 12 months after end of treatment. Treatment lasts 6-7 weeks. | The HHIA-S measures a person's perceived hearing handicap. Total score ranges from 0 to 40, with a higher score indicating more severe perceived hearing handicap, categorized as follows: * No handicap: 0-8. * Mild-moderate handicap: 10-24. * Severe handicap: 26-40. |
| Overall Survival by KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) Variant Status | From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 214 deaths were reported. Median follow-up at time of analysis was 8.3 years. | KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) is a gene that helps control how cells grow. Some people have a change in this gene, which can be detected (variant/non-variant) by a genetic test performed on tissue from their tumor. Research suggests that this change may influence how head and neck cancer responds to certain treatments. An event for overall survival is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is hazard ratio, which is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure. |
| Progression-free Survival by KRAS Variant Status | From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 214 deaths were reported. Median follow-up at time of analysis was 8.3 years. | KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) is a gene that helps control how cells grow. Some people have a change in this gene, which can be detected (variant/non-variant) by a genetic test performed on tissue from their tumor. Research suggests that this change may influence how head and neck cancer responds to certain treatments. An event for progression-free survival is local, regional, or distant disease progression or death due to any cause. Progression-free survival time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is the distribution of progression-free survival times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure. |
| Overall Survival by Treatment Arm Within KRAS Variant Status Group | From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 214 deaths were reported. Median follow-up at time of analysis was 8.3 years. | KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) is a gene that helps control how cells grow. Some people have a change in this gene, which can be detected (variant/non-variant) by a genetic test performed on tissue from their tumor. Research suggests that this change may influence how head and neck cancer responds to certain treatments. An event for overall survival is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is hazard ratio, which is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure. |
| Progression-free Survival Within KRAS Variant Status | From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 214 deaths were reported. Median follow-up at time of analysis was 8.3 years. | KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) is a gene that helps control how cells grow. Some people have a change in this gene, which can be detected (variant/non-variant) by a genetic test performed on tissue from their tumor. Research suggests that this change may influence how head and neck cancer responds to certain treatments. An event for progression-free survival is local, regional, or distant disease progression or death due to any cause. Progression-free survival time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is the distribution of progression-free survival times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure. |
Countries
Canada, United States
Contacts
PRINCIPAL_INVESTIGATORAndy M. Trotti, MD
H. Lee Moffitt Cancer Center and Research Institute
PRINCIPAL_INVESTIGATORMaura Gillison, MD, PhD
Ohio State University
Participant flow
Pre-assignment details
Sites were required to submit participant tumor tissue for central p16 evaluation within one week of registration. If participants were determined to be p16-positive and continued on the study, then treatment arm was assigned. Of 987 participants registered, 849 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| IMRT + Cisplatin Intensity-modulated radiotherapy (IMRT) with concurrent cisplatin
Cisplatin: 100 mg/m2 IV on days 1 and 22 of IMRT
IMRT: 35 fractions over 6 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 70 Gy. | 406 |
| IMRT + Cetuximab Intensity-modulated radiotherapy (IMRT) with concurrent cetuximab
Cetuximab: 400 mg/m2 IV 5-7 days before IMRT then 250 mg/m2 IV weekly for 7 weeks
IMRT: 35 fractions over 6 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 70 Gy. | 399 |
| Total | 805 |
Baseline characteristics
| Characteristic | IMRT + Cisplatin | Total | IMRT + Cetuximab |
|---|---|---|---|
| Age, Continuous | 58 years | 58 years | 58 years |
| Age, Customized <= 65 | 344 Participants | 689 Participants | 345 Participants |
| Age, Customized > 65 | 62 Participants | 116 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 26 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 383 Participants | 752 Participants | 369 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 12 Participants | 27 Participants | 15 Participants |
| Node category N0 | 20 Participants | 34 Participants | 14 Participants |
| Node category N1 | 20 Participants | 45 Participants | 25 Participants |
| Node category N2a | 59 Participants | 115 Participants | 56 Participants |
| Node category N2b | 209 Participants | 417 Participants | 208 Participants |
| Node category N2c | 82 Participants | 165 Participants | 83 Participants |
| Node category N3 | 16 Participants | 29 Participants | 13 Participants |
| Overall stage III | 29 Participants | 60 Participants | 31 Participants |
| Overall stage IV | 377 Participants | 745 Participants | 368 Participants |
| Primary site Base of tongue | 174 Participants | 353 Participants | 179 Participants |
| Primary site Oropharynx, not otherwise specified | 16 Participants | 31 Participants | 15 Participants |
| Primary site Pharyngeal oropharynx | 8 Participants | 13 Participants | 5 Participants |
| Primary site Soft palate | 4 Participants | 4 Participants | 0 Participants |
| Primary site Tonsillar fossa, tonsil | 202 Participants | 401 Participants | 199 Participants |
| Primary site Vallecula | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 17 Participants | 36 Participants | 19 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 10 Participants | 8 Participants |
| Race/Ethnicity, Customized Unknown | 7 Participants | 12 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 380 Participants | 747 Participants | 367 Participants |
| Risk group per study RTOG-0129 Intermediate risk | 117 Participants | 232 Participants | 115 Participants |
| Risk group per study RTOG-0129 Low risk | 289 Participants | 573 Participants | 284 Participants |
| Sex: Female, Male Female | 33 Participants | 77 Participants | 44 Participants |
| Sex: Female, Male Male | 373 Participants | 728 Participants | 355 Participants |
| Smoking history 0 pack-years | 194 Participants | 375 Participants | 181 Participants |
| Smoking history >0 to <= 10 pack-years | 59 Participants | 127 Participants | 68 Participants |
| Smoking history >10 pack-years | 153 Participants | 303 Participants | 150 Participants |
| Smoking history | 2 pack-years | 2 pack-years | 3 pack-years |
| Tumor stage T1 | 89 Participants | 175 Participants | 86 Participants |
| Tumor stage T2 | 162 Participants | 325 Participants | 163 Participants |
| Tumor stage T3 | 108 Participants | 208 Participants | 100 Participants |
| Tumor stage T4 | 47 Participants | 97 Participants | 50 Participants |
| Zubrod performance status 0 | 295 Participants | 595 Participants | 300 Participants |
| Zubrod performance status 1 | 111 Participants | 210 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 64 / 406 | 86 / 399 |
| other Total, other adverse events | 398 / 398 | 393 / 394 |
| serious Total, serious adverse events | 177 / 398 | 115 / 394 |
Outcome results
Primary
Overall Survival
An event for overall survival is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is hazard ratio, which is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.
Time frame: From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Overall Survival | 84.6 percentage of participants |
| IMRT + Cetuximab | Overall Survival | 77.9 percentage of participants |
Secondary
Distribution of First Progression Events
The first event type for progression-free survival is counted for each participant. Possible first progression events are local, regional, or distant progression, any combination of these, or death. The frequency table of these events is also referred to as Pattern of failure.
Time frame: From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years.
Population: Eligible participants with progression-free survival failure
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IMRT + Cisplatin | Distribution of First Progression Events | Local and distant | 0 Participants |
| IMRT + Cisplatin | Distribution of First Progression Events | Distant | 31 Participants |
| IMRT + Cisplatin | Distribution of First Progression Events | Local and regional | 4 Participants |
| IMRT + Cisplatin | Distribution of First Progression Events | Death, due to this disease | 2 Participants |
| IMRT + Cisplatin | Distribution of First Progression Events | Regional and distant | 0 Participants |
| IMRT + Cisplatin | Distribution of First Progression Events | Death, due to second primary | 1 Participants |
| IMRT + Cisplatin | Distribution of First Progression Events | Regional | 6 Participants |
| IMRT + Cisplatin | Distribution of First Progression Events | Death, due to other reason | 10 Participants |
| IMRT + Cisplatin | Distribution of First Progression Events | Local, regional, and distant | 0 Participants |
| IMRT + Cisplatin | Distribution of First Progression Events | Death, due to unknown reason | 9 Participants |
| IMRT + Cisplatin | Distribution of First Progression Events | Local | 13 Participants |
| IMRT + Cetuximab | Distribution of First Progression Events | Death, due to unknown reason | 10 Participants |
| IMRT + Cetuximab | Distribution of First Progression Events | Local | 25 Participants |
| IMRT + Cetuximab | Distribution of First Progression Events | Regional | 14 Participants |
| IMRT + Cetuximab | Distribution of First Progression Events | Local and regional | 8 Participants |
| IMRT + Cetuximab | Distribution of First Progression Events | Local and distant | 1 Participants |
| IMRT + Cetuximab | Distribution of First Progression Events | Regional and distant | 5 Participants |
| IMRT + Cetuximab | Distribution of First Progression Events | Local, regional, and distant | 2 Participants |
| IMRT + Cetuximab | Distribution of First Progression Events | Distant | 43 Participants |
| IMRT + Cetuximab | Distribution of First Progression Events | Death, due to this disease | 0 Participants |
| IMRT + Cetuximab | Distribution of First Progression Events | Death, due to second primary | 3 Participants |
| IMRT + Cetuximab | Distribution of First Progression Events | Death, due to other reason | 11 Participants |
Secondary
EORTC QLQ-C30 Global Health Status Score Change From Baseline at 12 Months From End of Treatment
The EORTC QLQ-C30 Global Health Status score measures a cancer patient's perception of their overall health and well-being and ranges from 0 (worst) to 100 (best). A positive change from baseline indicates improvement.
Time frame: Baseline and 12 months from end of treatment. Treatment lasts 6-7 weeks
Population: Eligible participants enrolled to the quality of life (QOL) substudy who received protocol treatment and had outcome measure data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMRT + Cisplatin | EORTC QLQ-C30 Global Health Status Score Change From Baseline at 12 Months From End of Treatment | 3.15 score on a scale | Standard Deviation 23.42 |
| IMRT + Cetuximab | EORTC QLQ-C30 Global Health Status Score Change From Baseline at 12 Months From End of Treatment | 2.59 score on a scale | Standard Deviation 21.09 |
Secondary
EORTC QLQ-C30 Global Health Status Score Change From Baseline at 3 Months From End of Treatment
The EORTC QLQ-C30 Global Health Status score measures a cancer patient's perception of their overall health and well-being and ranges from 0 (worst) to 100 (best). A positive change from baseline indicates improvement.
Time frame: Baseline and 3 months from end of treatment. Treatment lasts 6-7 weeks.
Population: Eligible participants enrolled to the quality of life (QOL) substudy who received protocol treatment and had outcome measure data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMRT + Cisplatin | EORTC QLQ-C30 Global Health Status Score Change From Baseline at 3 Months From End of Treatment | -4.42 score on a scale | Standard Deviation 25.92 |
| IMRT + Cetuximab | EORTC QLQ-C30 Global Health Status Score Change From Baseline at 3 Months From End of Treatment | -7.51 score on a scale | Standard Deviation 22.46 |
Secondary
EORTC QLQ-C30 Global Health Status Score Change From Baseline at 6 Months From End of Treatment
The EORTC QLQ-C30 Global Health Status score measures a cancer patient's perception of their overall health and well-being and ranges from 0 (worst) to 100 (best). A positive change from baseline indicates improvement.
Time frame: Baseline and 6 months from end of treatment. Treatment lasts 6-7 weeks.
Population: Eligible participants enrolled to the quality of life (QOL) substudy who received protocol treatment and had outcome measure data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMRT + Cisplatin | EORTC QLQ-C30 Global Health Status Score Change From Baseline at 6 Months From End of Treatment | -0.57 score on a scale | Standard Deviation 25.01 |
| IMRT + Cetuximab | EORTC QLQ-C30 Global Health Status Score Change From Baseline at 6 Months From End of Treatment | -0.90 score on a scale | Standard Deviation 23.35 |
p-value: 0.5438t-test, 1 sided
Secondary
EORTC QLQ-C30 Global Health Status Score Change From Baseline at End of Treatment
The EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30) Global Health Status score measures a cancer patient's perception of their overall health and well-being and ranges from 0 (worst) to 100 (best). A positive change from baseline indicates improvement.
Time frame: Baseline and end of treatment (6-7 weeks)
Population: Eligible participants enrolled to the quality of life (QOL) substudy who received protocol treatment and had outcome measure data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMRT + Cisplatin | EORTC QLQ-C30 Global Health Status Score Change From Baseline at End of Treatment | -23.16 score on a scale | Standard Deviation 28.16 |
| IMRT + Cetuximab | EORTC QLQ-C30 Global Health Status Score Change From Baseline at End of Treatment | -25.31 score on a scale | Standard Deviation 22.92 |
Secondary
EORTC QLQ-H&N35 Swallowing Score Change From Baseline at 12 Months From End of Treatment.
The EORTC QLQ-H&N35 swallowing score measures patient-reported difficulty with swallowing various foods and liquid and ranges from 0 (no swallowing problems) to 100 (maximum swallowing difficulty). A positive change from baseline indicates worsening swallowing function.
Time frame: Baseline and 12 months from end of treatment. Treatment lasts 6-7 weeks.
Population: Eligible participants enrolled to the quality of life (QOL) substudy who received protocol treatment and had outcome measure data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMRT + Cisplatin | EORTC QLQ-H&N35 Swallowing Score Change From Baseline at 12 Months From End of Treatment. | 2.52 score on a scale | Standard Deviation 19.64 |
| IMRT + Cetuximab | EORTC QLQ-H&N35 Swallowing Score Change From Baseline at 12 Months From End of Treatment. | 7.61 score on a scale | Standard Deviation 17.81 |
Secondary
EORTC QLQ-H&N35 Swallowing Score Change From Baseline at 3 Months From End of Treatment.
The EORTC QLQ-H&N35 swallowing score measures patient-reported difficulty with swallowing various foods and liquid and ranges from 0 (no swallowing problems) to 100 (maximum swallowing difficulty). A positive change from baseline indicates worsening swallowing function.
Time frame: Baseline and 3 months from end of treatment. Treatment lasts 6-7 weeks.
Population: Eligible participants enrolled to the quality of life (QOL) substudy who received protocol treatment and had outcome measure data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMRT + Cisplatin | EORTC QLQ-H&N35 Swallowing Score Change From Baseline at 3 Months From End of Treatment. | 10.58 score on a scale | Standard Deviation 26.49 |
| IMRT + Cetuximab | EORTC QLQ-H&N35 Swallowing Score Change From Baseline at 3 Months From End of Treatment. | 14.20 score on a scale | Standard Deviation 20.61 |
Secondary
EORTC QLQ-H&N35 Swallowing Score Change From Baseline at 6 Months From End of Treatment.
The EORTC QLQ-H&N35 swallowing score measures patient-reported difficulty with swallowing various foods and liquid and ranges from 0 (no swallowing problems) to 100 (maximum swallowing difficulty). A positive change from baseline indicates worsening swallowing function.
Time frame: Baseline and 6 months from end of treatment. Treatment lasts 6-7 weeks.
Population: Eligible participants enrolled to the quality of life (QOL) substudy who received protocol treatment and had outcome measure data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMRT + Cisplatin | EORTC QLQ-H&N35 Swallowing Score Change From Baseline at 6 Months From End of Treatment. | 8.65 score on a scale | Standard Deviation 23.94 |
| IMRT + Cetuximab | EORTC QLQ-H&N35 Swallowing Score Change From Baseline at 6 Months From End of Treatment. | 10.13 score on a scale | Standard Deviation 18.73 |
p-value: 0.7108t-test, 1 sided
Secondary
EORTC QLQ-H&N35 Swallowing Score Change From Baseline at End of Treatment
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Head and Neck Cancer Module (EORTC QLQ-H&N35) swallowing score measures patient-reported difficulty with swallowing various foods and liquid and ranges from 0 (no swallowing problems) to 100 (maximum swallowing difficulty). A positive change from baseline indicates worsening swallowing function.
Time frame: Baseline and end of treatment (6-7 weeks)
Population: Eligible participants enrolled to the quality of life (QOL) substudy who received protocol treatment and had outcome measure data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMRT + Cisplatin | EORTC QLQ-H&N35 Swallowing Score Change From Baseline at End of Treatment | 47.99 score on a scale | Standard Deviation 27.99 |
| IMRT + Cetuximab | EORTC QLQ-H&N35 Swallowing Score Change From Baseline at End of Treatment | 47.43 score on a scale | Standard Deviation 24.52 |
Secondary
EuroQol Five Dimension Scale (EQ-5D) at Baseline, End of Treatment, 3, 6, and 12 Months From End of Treatment.
Time frame: From randomization to 1 year after end of treatment.
Secondary
Number of Participants by HHIA-S Category at 12 Months After End of Treatment
The HHIA-S measures a person's perceived hearing handicap. Total score ranges from 0 to 40, with a higher score indicating more severe perceived hearing handicap, categorized as follows: * No handicap: 0-8. * Mild-moderate handicap: 10-24. * Severe handicap: 26-40.
Time frame: 12 months after end of treatment. Treatment lasts 6-7 weeks.
Population: Eligible participants enrolled to the quality of life (QOL) substudy who received protocol treatment and had outcome measure data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IMRT + Cisplatin | Number of Participants by HHIA-S Category at 12 Months After End of Treatment | No handicap | 84 Participants |
| IMRT + Cisplatin | Number of Participants by HHIA-S Category at 12 Months After End of Treatment | Mild-moderate handicap | 27 Participants |
| IMRT + Cisplatin | Number of Participants by HHIA-S Category at 12 Months After End of Treatment | Severe handicap | 10 Participants |
| IMRT + Cetuximab | Number of Participants by HHIA-S Category at 12 Months After End of Treatment | No handicap | 103 Participants |
| IMRT + Cetuximab | Number of Participants by HHIA-S Category at 12 Months After End of Treatment | Mild-moderate handicap | 17 Participants |
| IMRT + Cetuximab | Number of Participants by HHIA-S Category at 12 Months After End of Treatment | Severe handicap | 5 Participants |
Secondary
Number of Participants by HHIA-S Category at 3 Months After End of Treatment
The HHIA-S measures a person's perceived hearing handicap. Total score ranges from 0 to 40, with a higher score indicating more severe perceived hearing handicap, categorized as follows: * No handicap: 0-8. * Mild-moderate handicap: 10-24. * Severe handicap: 26-40.
Time frame: 3 months after end of treatment. Treatment lasts 6-7 weeks.
Population: Eligible participants enrolled to the quality of life (QOL) substudy who received protocol treatment and had outcome measure data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IMRT + Cisplatin | Number of Participants by HHIA-S Category at 3 Months After End of Treatment | No handicap | 93 Participants |
| IMRT + Cisplatin | Number of Participants by HHIA-S Category at 3 Months After End of Treatment | Mild-moderate handicap | 28 Participants |
| IMRT + Cisplatin | Number of Participants by HHIA-S Category at 3 Months After End of Treatment | Severe handicap | 15 Participants |
| IMRT + Cetuximab | Number of Participants by HHIA-S Category at 3 Months After End of Treatment | No handicap | 109 Participants |
| IMRT + Cetuximab | Number of Participants by HHIA-S Category at 3 Months After End of Treatment | Mild-moderate handicap | 21 Participants |
| IMRT + Cetuximab | Number of Participants by HHIA-S Category at 3 Months After End of Treatment | Severe handicap | 7 Participants |
Secondary
Number of Participants by HHIA-S Category at 6 Months After End of Treatment
The HHIA-S measures a person's perceived hearing handicap. Total score ranges from 0 to 40, with a higher score indicating more severe perceived hearing handicap, categorized as follows: * No handicap: 0-8. * Mild-moderate handicap: 10-24. * Severe handicap: 26-40.
Time frame: 6 months after end of treatment. Treatment lasts 6-7 weeks.
Population: Eligible participants enrolled to the quality of life (QOL) substudy who received protocol treatment and had outcome measure data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IMRT + Cisplatin | Number of Participants by HHIA-S Category at 6 Months After End of Treatment | No handicap | 95 Participants |
| IMRT + Cisplatin | Number of Participants by HHIA-S Category at 6 Months After End of Treatment | Mild-moderate handicap | 31 Participants |
| IMRT + Cisplatin | Number of Participants by HHIA-S Category at 6 Months After End of Treatment | Severe handicap | 14 Participants |
| IMRT + Cetuximab | Number of Participants by HHIA-S Category at 6 Months After End of Treatment | No handicap | 106 Participants |
| IMRT + Cetuximab | Number of Participants by HHIA-S Category at 6 Months After End of Treatment | Mild-moderate handicap | 21 Participants |
| IMRT + Cetuximab | Number of Participants by HHIA-S Category at 6 Months After End of Treatment | Severe handicap | 4 Participants |
Secondary
Number of Participants by HHIA-S Category at Baseline
The Hearing Handicap Inventory for Adults Screen Version (HHIA-S) measures a person's perceived hearing handicap. Total score ranges from 0 to 40, with a higher score indicating more severe perceived hearing handicap, categorized as follows: * No handicap: 0-8. * Mild-moderate handicap: 10-24. * Severe handicap: 26-40.
Time frame: Baseline
Population: Eligible participants enrolled to the quality of life (QOL) substudy who received protocol treatment and had outcome measure data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IMRT + Cisplatin | Number of Participants by HHIA-S Category at Baseline | No handicap | 150 Participants |
| IMRT + Cisplatin | Number of Participants by HHIA-S Category at Baseline | Mild-moderate handicap | 23 Participants |
| IMRT + Cisplatin | Number of Participants by HHIA-S Category at Baseline | Severe handicap | 2 Participants |
| IMRT + Cetuximab | Number of Participants by HHIA-S Category at Baseline | No handicap | 132 Participants |
| IMRT + Cetuximab | Number of Participants by HHIA-S Category at Baseline | Mild-moderate handicap | 32 Participants |
| IMRT + Cetuximab | Number of Participants by HHIA-S Category at Baseline | Severe handicap | 7 Participants |
Secondary
Number of Participants by HHIA-S Category at End of Treatment
The Hearing Handicap Inventory for Adults Screen Version (HHIA-S) measures a person's perceived hearing handicap. Total score ranges from 0 to 40, with a higher score indicating more severe perceived hearing handicap, categorized as follows: * No handicap: 0-8. * Mild-moderate handicap: 10-24. * Severe handicap: 26-40.
Time frame: End of treatment (6-7 weeks)
Population: Eligible participants enrolled to the quality of life (QOL) substudy who received protocol treatment and had outcome measure data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IMRT + Cisplatin | Number of Participants by HHIA-S Category at End of Treatment | No handicap | 91 Participants |
| IMRT + Cisplatin | Number of Participants by HHIA-S Category at End of Treatment | Mild-moderate handicap | 29 Participants |
| IMRT + Cisplatin | Number of Participants by HHIA-S Category at End of Treatment | Severe handicap | 14 Participants |
| IMRT + Cetuximab | Number of Participants by HHIA-S Category at End of Treatment | No handicap | 107 Participants |
| IMRT + Cetuximab | Number of Participants by HHIA-S Category at End of Treatment | Mild-moderate handicap | 21 Participants |
| IMRT + Cetuximab | Number of Participants by HHIA-S Category at End of Treatment | Severe handicap | 5 Participants |
Secondary
Overall Survival by KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) Variant Status
KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) is a gene that helps control how cells grow. Some people have a change in this gene, which can be detected (variant/non-variant) by a genetic test performed on tissue from their tumor. Research suggests that this change may influence how head and neck cancer responds to certain treatments. An event for overall survival is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is hazard ratio, which is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.
Time frame: From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 214 deaths were reported. Median follow-up at time of analysis was 8.3 years.
Population: Eligible participants with KRAS data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Overall Survival by KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) Variant Status | 80.6 percentage of participants |
| IMRT + Cetuximab | Overall Survival by KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) Variant Status | 79.2 percentage of participants |
p-value: 0.257195% CI: [0.56, 1.34]Regression, Cox
Secondary
Overall Survival by Treatment Arm Within KRAS Variant Status Group
KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) is a gene that helps control how cells grow. Some people have a change in this gene, which can be detected (variant/non-variant) by a genetic test performed on tissue from their tumor. Research suggests that this change may influence how head and neck cancer responds to certain treatments. An event for overall survival is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is hazard ratio, which is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.
Time frame: From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 214 deaths were reported. Median follow-up at time of analysis was 8.3 years.
Population: Eligible participants with KRAS data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IMRT + Cisplatin | Overall Survival by Treatment Arm Within KRAS Variant Status Group | Variant | 83.3 percentage of participants |
| IMRT + Cisplatin | Overall Survival by Treatment Arm Within KRAS Variant Status Group | Non-variant | 80.8 percentage of participants |
| IMRT + Cetuximab | Overall Survival by Treatment Arm Within KRAS Variant Status Group | Non-variant | 77.6 percentage of participants |
| IMRT + Cetuximab | Overall Survival by Treatment Arm Within KRAS Variant Status Group | Variant | 78.4 percentage of participants |
Comparison: Variant95% CI: [0.49, 2.46]
Comparison: Non-variant95% CI: [0.79, 1.53]
Comparison: Testing Cox proportional hazards model interaction term for KRAS variant status and treatment arm.p-value: 0.989Regression, Cox
Secondary
Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events for Head and Neck (PRO-CTCAE H&N) at Baseline, End of Treatment, 3, 6, and 12 Months From End of Treatment.
Time frame: From randomization to 1 year after end of treatment.
Secondary
Percentage of Participants Experiencing Early Death
Early death is defined as death due to adverse event or within 30 days of treatment completion.
Time frame: From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years.
Population: Eligible patients who started study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Percentage of Participants Experiencing Early Death | 1.5 percentage of participants |
| IMRT + Cetuximab | Percentage of Participants Experiencing Early Death | 1.5 percentage of participants |
p-value: 1Fisher Exact
Secondary
Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 1 Month After End of Study Treatment
Acute adverse events (AE) are defined as occurring within 180 days from the end of treatment. Treatment-related means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE
Time frame: From start of treatment to approximately 2.5 months (1 month after the end of treatment)
Population: Eligible patients who started study treatment and had adverse events assessment at 1 month after treatment end
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 1 Month After End of Study Treatment | 32.5 percentage of participants |
| IMRT + Cetuximab | Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 1 Month After End of Study Treatment | 31.1 percentage of participants |
Secondary
Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 3 Months After the End of Study Treatment
Acute adverse events (AE) are defined as occurring within 180 days from the end of treatment. Treatment-related means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE
Time frame: From start of treatment to approximately 4.5 months (3 months after the end of treatment)
Population: Eligible patients who started study treatment and had adverse events assessment at 3 months after treatment end
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 3 Months After the End of Study Treatment | 17.5 percentage of participants |
| IMRT + Cetuximab | Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 3 Months After the End of Study Treatment | 14.7 percentage of participants |
Secondary
Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 6 Months After the End of Study Treatment
Acute adverse events (AE) are defined as occurring within 180 days from the end of treatment. Treatment-related means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE
Time frame: From start of treatment to approximately 7.5 months (6 months after the end of treatment)
Population: Eligible patients who started study treatment and had adverse events assessment at 6 months year after treatment end
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 6 Months After the End of Study Treatment | 13.3 percentage of participants |
| IMRT + Cetuximab | Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 6 Months After the End of Study Treatment | 9.4 percentage of participants |
Secondary
Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: During Treatment
Acute adverse events (AE) are defined as occurring within 180 days from the end of treatment. Treatment-related means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE
Time frame: From start of treatment to end of treatment, approximately 6 weeks
Population: All eligible patients who started study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: During Treatment | 75.6 percentage of participants |
| IMRT + Cetuximab | Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: During Treatment | 73.6 percentage of participants |
Secondary
Percentage of Participants With a Feeding Tube at 1 Year
Time frame: From randomization to 1 year.
Population: Eligible patients who started study treatment and had feeding tube assessment at 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Percentage of Participants With a Feeding Tube at 1 Year | 9.2 percentage of participants |
| IMRT + Cetuximab | Percentage of Participants With a Feeding Tube at 1 Year | 8.4 percentage of participants |
p-value: 0.79Fisher Exact
Secondary
Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 1 Year After the End of Study Treatment
Late adverse events (AE) are defined as \> 180 days from end of treatment. Treatment-related means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE
Time frame: From start of treatment to approximately 13.5 months (one year after the end of treatment)
Population: Eligible patients who started study treatment and had adverse events assessment at 1 year after treatment end
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 1 Year After the End of Study Treatment | 10.0 percentage of participants |
| IMRT + Cetuximab | Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 1 Year After the End of Study Treatment | 8.5 percentage of participants |
Secondary
Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 2 Years After the End of Study Treatment
Late adverse events (AE) are defined as \> 180 days from end of treatment. Treatment-related means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE
Time frame: From 180 days after end of treatment to two years after end of treatment.
Population: .Eligible patients who started study treatment and had adverse events assessment at 2 years after treatment end
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 2 Years After the End of Study Treatment | 7.7 percentage of participants |
| IMRT + Cetuximab | Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 2 Years After the End of Study Treatment | 4.0 percentage of participants |
Secondary
Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 5 Years After the End of Study Treatment
Late adverse events (AE) are defined as \> 180 days from end of treatment. Treatment-related means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE
Time frame: From start of treatment to approximately 61.5 months (five years after the end of treatment)
Population: Eligible patients who started study treatment and had adverse events assessment at 5 years after treatment end
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 5 Years After the End of Study Treatment | 4.3 percentage of participants |
| IMRT + Cetuximab | Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 5 Years After the End of Study Treatment | 7.0 percentage of participants |
Secondary
Percentage of Patients With Normal/Good Dental Health: 10 Years After End of Treatment
This study utilized a dental effects health scale from 0 (normal) to 4 (life-threatening dental condition). The percentage of participants with a value of 0 or 1 is reported: 0 = Normal: Edentulous, with no gingival disease; 1 = Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; \< 5 restorations indicated; no extractions indicated.
Time frame: 10 years after end of treatment (approximately 121.5 months)
Population: Eligible patients who started study treatment and had dental status assessment at 10 years after treatment end
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Percentage of Patients With Normal/Good Dental Health: 10 Years After End of Treatment | 91.2 Percentage of participants |
| IMRT + Cetuximab | Percentage of Patients With Normal/Good Dental Health: 10 Years After End of Treatment | 84.0 Percentage of participants |
Secondary
Percentage of Patients With Normal/Good Dental Health: 1 Year After End of Treatment
This study utilized a dental effects health scale from 0 (normal) to 4 (life-threatening dental condition). The percentage of participants with a value of 0 or 1 is reported: 0 = Normal: Edentulous, with no gingival disease; 1 = Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; \< 5 restorations indicated; no extractions indicated.
Time frame: 1 year after end of treatment (approximately 13.5 months)
Population: Eligible patients who started study treatment and had dental status assessment at 1 year after treatment end
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Percentage of Patients With Normal/Good Dental Health: 1 Year After End of Treatment | 87.3 percentage of participants |
| IMRT + Cetuximab | Percentage of Patients With Normal/Good Dental Health: 1 Year After End of Treatment | 83.5 percentage of participants |
Secondary
Percentage of Patients With Normal/Good Dental Health: 2 Years After End of Treatment
This study utilized a dental effects health scale from 0 (normal) to 4 (life-threatening dental condition). The percentage of participants with a value of 0 or 1 is reported: 0 = Normal: Edentulous, with no gingival disease; 1 = Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; \< 5 restorations indicated; no extractions indicated.
Time frame: 2 years after end of treatment (approximately 25.5 months)
Population: Eligible patients who started study treatment and had dental status assessment at 2 years after treatment end
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Percentage of Patients With Normal/Good Dental Health: 2 Years After End of Treatment | 86.5 percentage of participants |
| IMRT + Cetuximab | Percentage of Patients With Normal/Good Dental Health: 2 Years After End of Treatment | 82.1 percentage of participants |
Secondary
Percentage of Patients With Normal/Good Dental Health: 5 Years After End of Treatment
This study utilized a dental effects health scale from 0 (normal) to 4 (life-threatening dental condition). The percentage of participants with a value of 0 or 1 is reported: 0 = Normal: Edentulous, with no gingival disease; 1 = Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; \< 5 restorations indicated; no extractions indicated.
Time frame: 5 years after end of treatment (approximately 61.5 months)
Population: Eligible patients who started study treatment and had dental status assessment at 5 years after treatment end
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Percentage of Patients With Normal/Good Dental Health: 5 Years After End of Treatment | 88.6 percentage of participants |
| IMRT + Cetuximab | Percentage of Patients With Normal/Good Dental Health: 5 Years After End of Treatment | 86.0 percentage of participants |
Secondary
Percentage of Patients With Normal/Good Dental Health: Pretreatment
This study utilized a dental effects health scale from 0 (normal) to 4 (life-threatening dental condition). The percentage of participants with a value of 0 or 1 is reported: 0 = Normal: Edentulous, with no gingival disease; 1 = Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; \< 5 restorations indicated; no extractions indicated. Ten year data is not yet available.
Time frame: Before treatment
Population: Eligible patients who started study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Percentage of Patients With Normal/Good Dental Health: Pretreatment | 71.1 percentage of participants |
| IMRT + Cetuximab | Percentage of Patients With Normal/Good Dental Health: Pretreatment | 74.6 percentage of participants |
Secondary
Progression-free Survival
An event for progression-free survival is local, regional, or distant disease progression or death due to any cause. Progression-free survival time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is the distribution of progression-free survival times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.
Time frame: From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Progression-free Survival | 78.4 percentage of participants |
| IMRT + Cetuximab | Progression-free Survival | 67.3 percentage of participants |
p-value: 0.000295% CI: [1.29, 2.29]Log Rank
Secondary
Progression-free Survival by KRAS Variant Status
KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) is a gene that helps control how cells grow. Some people have a change in this gene, which can be detected (variant/non-variant) by a genetic test performed on tissue from their tumor. Research suggests that this change may influence how head and neck cancer responds to certain treatments. An event for progression-free survival is local, regional, or distant disease progression or death due to any cause. Progression-free survival time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is the distribution of progression-free survival times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.
Time frame: From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 214 deaths were reported. Median follow-up at time of analysis was 8.3 years.
Population: Eligible participants with KRAS data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Progression-free Survival by KRAS Variant Status | 72.0 percentage of participants |
| IMRT + Cetuximab | Progression-free Survival by KRAS Variant Status | 71.5 percentage of participants |
p-value: 0.370495% CI: [0.64, 1.38]Regression, Cox
Secondary
Progression-free Survival Within KRAS Variant Status
KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) is a gene that helps control how cells grow. Some people have a change in this gene, which can be detected (variant/non-variant) by a genetic test performed on tissue from their tumor. Research suggests that this change may influence how head and neck cancer responds to certain treatments. An event for progression-free survival is local, regional, or distant disease progression or death due to any cause. Progression-free survival time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is the distribution of progression-free survival times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.
Time frame: From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 214 deaths were reported. Median follow-up at time of analysis was 8.3 years.
Population: Eligible participants with KRAS data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IMRT + Cisplatin | Progression-free Survival Within KRAS Variant Status | Non-variant | 75.1 percentage of participants |
| IMRT + Cisplatin | Progression-free Survival Within KRAS Variant Status | Variant | 76.6 percentage of participants |
| IMRT + Cetuximab | Progression-free Survival Within KRAS Variant Status | Variant | 67.7 percentage of participants |
| IMRT + Cetuximab | Progression-free Survival Within KRAS Variant Status | Non-variant | 68.0 percentage of participants |
Comparison: Variant95% CI: [0.5, 2.04]
Comparison: Non-variant95% CI: [0.94, 1.73]
Comparison: Testing Cox proportional hazards model interaction term for KRAS variant status and treatment arm.p-value: 0.5556Regression, Cox
Secondary
Time to Distant Metastasis
Failure for distant metastasis endpoint was defined as distant progression; local-regional failure and death due to any cause were considered competing risks. Distant metastasis time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method. The protocol endpoint is the distribution of distant metastasis times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.
Time frame: From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Time to Distant Metastasis | 8.6 percentage of participants |
| IMRT + Cetuximab | Time to Distant Metastasis | 11.7 percentage of participants |
p-value: 0.0995% CI: [0.94, 2.36]Log Rank
Secondary
Time to Local-regional Failure
Failure for local-regional failure endpoint was defined as local or regional progression, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown \> 20 weeks after the end of radiation therapy, death due to study cancer without documented progression, or death due to unknown causes without documented progression; distant metastasis and death due to other causes were considered competing risks. Local-regional failure time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method. The protocol endpoint is the distribution of local-regional failure times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.
Time frame: From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Time to Local-regional Failure | 9.9 percentage of participants |
| IMRT + Cetuximab | Time to Local-regional Failure | 17.3 percentage of participants |
p-value: 0.000595% CI: [1.35, 3.1]Log Rank
Secondary
Time to Secondary Primary Cancer
Failure for second primary endpoint was defined as reporting of a new primary cancer; death due to any cause was considered a competing risk. Second primary time is defined as time from randomization to the date of second primary or last known follow-up (censored). Rates are estimated by the cumulative incidence method. The protocol endpoint is the distribution of second primary cancer times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.
Time frame: From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT + Cisplatin | Time to Secondary Primary Cancer | 9.9 percentage of participants |
| IMRT + Cetuximab | Time to Secondary Primary Cancer | 10.3 percentage of participants |
p-value: 0.9595% CI: [0.61, 1.58]Log Rank
Secondary
Work Status Questionnaire at Baseline, End of Treatment, 3, 6, and 12 Months.
Time frame: From randomization to 1 year after end of treatment.
Other Pre-specified
Overall Survival by Ethnicity
NIH-required analysis. An event for overall survival is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is hazard ratio, which is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.
Time frame: From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years.
Population: Eligible participants. Data were stratified by ethnicity.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IMRT + Cisplatin | Overall Survival by Ethnicity | Unknown or Not Reported | 66.8 percentage of participants |
| IMRT + Cisplatin | Overall Survival by Ethnicity | Hispanic or Latino | 100 percentage of participants |
| IMRT + Cisplatin | Overall Survival by Ethnicity | Not Hispanic or Latino | 84.7 percentage of participants |
| IMRT + Cetuximab | Overall Survival by Ethnicity | Hispanic or Latino | 70.7 percentage of participants |
| IMRT + Cetuximab | Overall Survival by Ethnicity | Not Hispanic or Latino | 77.9 percentage of participants |
| IMRT + Cetuximab | Overall Survival by Ethnicity | Unknown or Not Reported | 85.7 percentage of participants |
Other Pre-specified
Overall Survival by Race
NIH-required analysis. An event for overall survival is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is hazard ratio, which is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.
Time frame: From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years. Five-year rates are reported here.
Population: Eligible participants. Data were stratified by ethnicity.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IMRT + Cisplatin | Overall Survival by Race | Asian | NA percentage of participants |
| IMRT + Cisplatin | Overall Survival by Race | Black or African American | 77.5 percentage of participants |
| IMRT + Cisplatin | Overall Survival by Race | Unknown or Not Reported | 100 percentage of participants |
| IMRT + Cisplatin | Overall Survival by Race | White | 84.6 percentage of participants |
| IMRT + Cetuximab | Overall Survival by Race | Native Hawaiian or Other Pacific Islander | NA percentage of participants |
| IMRT + Cetuximab | Overall Survival by Race | Black or African American | 76.4 percentage of participants |
| IMRT + Cetuximab | Overall Survival by Race | More than one race | NA percentage of participants |
| IMRT + Cetuximab | Overall Survival by Race | Unknown or Not Reported | 100 percentage of participants |
| IMRT + Cetuximab | Overall Survival by Race | White | 77.3 percentage of participants |
| IMRT + Cetuximab | Overall Survival by Race | American Indian or Alaska Native | 100 percentage of participants |
| IMRT + Cetuximab | Overall Survival by Race | Asian | 100 percentage of participants |
Other Pre-specified
Overall Survival by Sex
NIH-required analysis. An event for overall survival is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is hazard ratio, which is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.
Time frame: From randomization to last follow-up. Analysis was to occur after 180 deaths were reported. Analysis occurred after 133 deaths were reported. Maximum follow-up at time of analysis was 6.5 years.
Population: Eligible participants. Data were stratified by sex.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IMRT + Cisplatin | Overall Survival by Sex | Female | 93.4 percentage of participants |
| IMRT + Cisplatin | Overall Survival by Sex | Male | 83.8 percentage of participants |
| IMRT + Cetuximab | Overall Survival by Sex | Female | 76.8 percentage of participants |
| IMRT + Cetuximab | Overall Survival by Sex | Male | 78.0 percentage of participants |