Esophageal Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Stage IB Esophageal Cancer AJCC v7, Stage IIA Esophageal Cancer AJCC v7, Stage IIB Esophageal Cancer AJCC v7, Stage IIIA Esophageal Cancer AJCC v7, Stage IIIB Esophageal Cancer AJCC v7
Conditions
Brief summary
This randomized phase III trial studies how well radiation therapy, paclitaxel, and carboplatin with or without trastuzumab work in treating patients with esophageal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving radiation therapy and combination chemotherapy together with or without trastuzumab is more effective in treating esophageal cancer.
Detailed description
PRIMARY OBJECTIVES: l. To determine if trastuzumab increases disease-free survival when combined with trimodality treatment (radiation plus chemotherapy followed by surgery) for patients with human epidermal growth factor receptor 2 (HER2)-overexpressing esophageal adenocarcinoma. SECONDARY OBJECTIVES: I. To evaluate if the addition of trastuzumab to trimodality treatment increases the pathologic complete response rate and overall survival for patients with HER2-overexpressing esophageal adenocarcinoma. II. To develop a tissue bank of tumor tissue from patients with non-metastatic esophageal adenocarcinoma. III. To determine molecular correlates of complete pathologic response, disease-free survival, and overall survival for patients with HER2-overexpressing esophageal adenocarcinoma treated with neoadjuvant and maintenance trastuzumab. IV. To evaluate predictors of cardiotoxicity in patients with esophageal cancer treated with trastuzumab and chemoradiation. V. To evaluate adverse events associated with the addition of trastuzumab to trimodality treatment for patients with non-metastatic esophageal adenocarcinoma. PATIENT-REPORTED QUALITY OF LIFE OBJECTIVES: I. To determine if the addition of trastuzumab to trimodality treatment improves the patient-reported Functional Assessment of Cancer Therapy for Esophageal Cancer (FACT-E) Esophageal Cancer Subscale (ECS) score. II. To determine if an improvement in the FACT-E ECS score at 6-8 weeks post completion of neoadjuvant chemoradiation correlates with pathologic complete response. III. To determine if pathologic complete response correlates with the FACT-E ECS score at 1 year and/or 2 years from the start of chemoradiation. IV. To determine if the addition of trastuzumab to trimodality treatment improves the Swallow Index and Eating Index Subscale scores of the FACT-E. V. To determine if the addition of trastuzumab to paclitaxel, carboplatin, and radiation impacts quality-adjusted survival. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive trastuzumab intravenously (IV) over 30-90 minutes on days 1, 8, 15, 22, 29, 36, and 57 and paclitaxel IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Beginning 21-56 days after surgery, patients receive trastuzumab IV over 30-90 minutes. Treatment repeats every 21 days for 13 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive paclitaxel IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Within 5-8 weeks after completion of radiotherapy, all patients undergo surgery. After completion of study therapy, patients are followed up every 4 months for 2 years and then yearly thereafter.
Interventions
DRUGCarboplatin
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGPaclitaxel
Given IV
OTHERQuality-of-Life Assessment
Ancillary studies
RADIATIONRadiation Therapy
Undergo radiation therapy
PROCEDURETherapeutic Conventional Surgery
Undergo surgery
BIOLOGICALTrastuzumab
Given IV
Sponsors
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically confirmed primary adenocarcinoma of the esophagus that involves the mid (up to 25 cm), distal, or esophagogastric junction; the cancer may involve the stomach up to 5 cm * Endoscopy with biopsy * PRIOR TO STEP 1 REGISTRATION BUT WITHIN 56 DAYS PRIOR TO STEP 2 REGISTRATION * Intent to submit tissue for central HER2 testing * Stage T1N1-2, T2-3N0-2, according to the American Joint Committee on Cancer (AJCC) 7th edition staging, based on the following minimum diagnostic work-up: * Chest/abdominal/pelvic computed tomography (CT) or whole-body positron emission tomography (PET)/CT (NOTE: if CT is performed at this time point, whole-body PET/CT will be required prior to step 2 registration; PET/CT of skull base to mid-thigh is acceptable) (NOTE: if adenopathy is noted on CT or whole-body PET/CT scan, an endoscopic ultrasound is not required prior to STEP 2 registration as long as adequate tissue has been obtained for central HER2 testing) * Patients may have regional adenopathy including para-esophageal, gastric, gastrohepatic and celiac nodes; if celiac adenopathy is present, it must be =\< 2 cm * Patients with tumors at the level of the carina or above must undergo bronchoscopy to exclude fistula * Zubrod performance status 0-2 * Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 * Platelets \>= 100,000 cells/mm\^3 * Hemoglobin \>= 8.0 g/dL (note: the use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 8.0 g/dL is acceptable) * Creatinine =\< 2 times upper limit of normal * Bilirubin =\< 1.5 times upper limit of normal * Aspartate aminotransferase (AST) =\< 3.0 times upper limit of normal * For women of childbearing potential, a negative serum or urine pregnancy test * Patients must sign a study-specific informed consent prior to study entry * CONDITIONS FOR PATIENT ELIGIBILITY PRIOR TO STEP 2 REGISTRATION (HER2-POSITIVE PATIENTS ONLY) * HER2 expressing adenocarcinoma of the esophagus centrally * Surgical consultation to confirm that patient will be able to undergo curative resection after completion of chemoradiation within 56 days prior to step 2 registration * Radiation oncology consultation to confirm that disease can be encompassed in a radiotherapy field within 56 days prior to step 2 registration * Consultation with a medical oncologist within 56 days prior to step 2 registration * Stage T1N1-2, T2-3N0-2, according to the AJCC 7th edition staging, based upon the following minimum diagnostic work-up: * History/physical examination, with documentation of the patient's weight, within 14 days prior to step 2 registration * Whole-body PET/CT scan within 56 days prior to step 2 registration (if only CT performed prior to step 1 registration) * Endoscopic ultrasound within 56 days prior to step 2 registration, unless the patient is found to have adenopathy per CT or whole-body PET/CT scan * Electrocardiogram (EKG) within 56 days prior to step 2 registration * Serum creatinine =\< 2 x the upper limit or normal within 14 days prior to step 2 registration * Zubrod performance status 0-2 within 14 days prior to step 2 registration * For women of childbearing potential, a negative serum pregnancy test within 14 days prior to step 2 registration * Left ventricular ejection fraction (LVEF) \>= institutional lower limit of normal by cardiac echocardiogram (echo) or multi gated acquisition (MUGA) scan within 56 days prior to step 2 registration * Women of childbearing potential and sexually active male participants must agree to practice adequate contraception while on study and for at least 60 days following the last dose of chemotherapy or trastuzumab
Exclusion criteria
* Patients with cervical esophageal carcinoma * Patients with T1N0 disease, T4 disease, and proximal esophageal cancers (15-24 cm) * Prior systemic chemotherapy for esophageal cancer; note that prior chemotherapy for a different cancer is allowable * Prior radiation therapy for esophageal cancer or prior chest radiotherapy * Prior anthracycline or taxane * Evidence of tracheoesophageal fistula or invasion into the trachea or major bronchi * Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 2 years (e.g., carcinoma in situ of the breast, oral cavity, or cervix are permissible) * Medical contraindications to esophagectomy * Prior therapy with any agent targeting the HER2 pathway or human epidermal growth factor receptor 1 (HER1) (epidermal growth factor receptor \[EGFR\]) pathway * Prior therapy with trastuzumab * Prior allergic reaction to the study drugs involved in this protocol or to a monoclonal antibody * Previous history of congestive heart failure * Severe, active comorbidity, defined as follows: * Unstable angina in the last 6 months * Transmural myocardial infarction within the last 6 months * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration * Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immunocompromised patients * Pregnant or nursing women or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (DFS) | From randomization to last follow-up. Maximum follow-up at time of analysis was 8.0 years. | A disease event is defined as local/regional persistence or recurrence of the cancer under study, distant metastases, a new second primary cancer, or death due to any cause. Participants undergoing surgery who had an R2 resection and participants not undergoing surgery who had a positive endoscopic biopsy or no biopsy at all were considered to have local persistence of disease. Disease-free survival time is defined as time from randomization to the date of first disease event or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis was to occur after 162 events were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Pathologic Complete Response at Surgery | At the time of surgery, 5-8 weeks after completion of radiation therapy. | Pathologic Complete Response (pCR) is evaluated after surgery and is based on the pathology review of the submitted surgical specimen. Pathologic Complete Response occurs if the pathologist determines that the resected esophageal specimen, accompanying lymph nodes, and surgical margins are all free of tumor. |
| Overall Survival | From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years. | Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis occurred after 109 deaths were reported. |
| Frequency of Highest Grade Adverse Event Per Participant | From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years. | Common Terminology Criteria for Adverse Events (version 4.0 before 4-1-2018; then version 5.0) grades adverse event severity from 1=mild to 5=death. Summary data provided is in this outcome measure; see Adverse Events Module for specific adverse event data. |
| Percentage of Patients With Improvement in the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) Esophageal Cancer Subscale (ECS) Subscale After Treatment | Baseline, 6-8 weeks after end of radiation therapy (approximately 11.5-13.5 weeks from treatment start), 1 and 2 years from treatment start | The ECS is a 17-item self-report instrument designed to measure multidimensional quality of life in patients with esophagus cancer with a total score ranging from 0-68. It is to be administered with the Functional Assessment of Cancer Therapy - General (FACT-G). A higher score indicates better QOL. Improvement is defined as an increase from the baseline score of at least 5 points. |
| Quality-adjusted Survival | From randomization to last follow-up. Maximum follow-up at time of primary outcome measure analysis was 8 years. | — |
| Molecular Correlates of Efficacy | From randomization to last follow-up. Maximum follow-up at time of primary outcome measure analysis was 8 years. | — |
| Number of Participants With Any Cardiac Adverse Events Regardless of Attribution | From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years. | Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event (AE) severity from 1=mild to 5=death. Logistic regression was used to evaluate treatment arm, clinical tumor stage (T stage), Zubrod Performance Status, gender, presence of adenopathy, and age as possible predictors of cardiac adverse events. Results of the final model are reported in the statistical analysis section. Summary adverse event data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORHoward P Safran
NRG Oncology
Participant flow
Pre-assignment details
After registration, sites were required to submit participant tumor tissue for central human epidermal growth factor receptor 2 (HER2) testing. Only HER2-positive participants continued to randomization. In total, 571 participants were registered and 203 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Chemoradiation and Trastuzumab Radiation therapy with concurrent trastuzumab, paclitaxel, and carboplatin followed by surgery followed by maintenance trastuzumab | 98 |
| Chemoradiation Radiation therapy with concurrent paclitaxel and carboplatin followed by surgery | 96 |
| Total | 194 |
Baseline characteristics
| Characteristic | Chemoradiation and Trastuzumab | Chemoradiation | Total |
|---|---|---|---|
| Age, Customized ≤ 39 years | 0 Participants | 5 Participants | 5 Participants |
| Age, Customized 40-49 years | 6 Participants | 7 Participants | 13 Participants |
| Age, Customized 50-59 years | 30 Participants | 21 Participants | 51 Participants |
| Age, Customized 60-69 years | 40 Participants | 31 Participants | 71 Participants |
| Age, Customized 70-79 years | 20 Participants | 29 Participants | 49 Participants |
| Age, Customized ≥ 80 years | 2 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 5 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 96 Participants | 89 Participants | 185 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| N stage, clinical N0 | 27 Participants | 29 Participants | 56 Participants |
| N stage, clinical N1 | 55 Participants | 48 Participants | 103 Participants |
| N stage, clinical N2 | 16 Participants | 19 Participants | 35 Participants |
| Presence of Adenopathy No | 38 Participants | 38 Participants | 76 Participants |
| Presence of Adenopathy Yes adenopathy and celiac present ≤ 2 cm | 12 Participants | 10 Participants | 22 Participants |
| Presence of Adenopathy Yes adenopathy, but celiac absent | 48 Participants | 48 Participants | 96 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 94 Participants | 92 Participants | 186 Participants |
| Sex: Female, Male Female | 13 Participants | 17 Participants | 30 Participants |
| Sex: Female, Male Male | 85 Participants | 79 Participants | 164 Participants |
| T stage, clinical T1 | 1 Participants | 4 Participants | 5 Participants |
| T stage, clinical T2 | 18 Participants | 17 Participants | 35 Participants |
| T stage, clinical T3 | 79 Participants | 75 Participants | 154 Participants |
| Zubrod Performance Status 0 | 62 Participants | 62 Participants | 124 Participants |
| Zubrod Performance Status 1 | 34 Participants | 31 Participants | 65 Participants |
| Zubrod Performance Status 2 | 2 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 53 / 95 | 55 / 96 |
| other Total, other adverse events | 95 / 95 | 96 / 96 |
| serious Total, serious adverse events | 51 / 95 | 34 / 96 |
Outcome results
Primary
Disease-free Survival (DFS)
A disease event is defined as local/regional persistence or recurrence of the cancer under study, distant metastases, a new second primary cancer, or death due to any cause. Participants undergoing surgery who had an R2 resection and participants not undergoing surgery who had a positive endoscopic biopsy or no biopsy at all were considered to have local persistence of disease. Disease-free survival time is defined as time from randomization to the date of first disease event or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis was to occur after 162 events were reported.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 8.0 years.
Population: Eligible randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemoradiation and Trastuzumab (Arm 1) | Disease-free Survival (DFS) | 19.6 months |
| Chemoradiation (Arm 2) | Disease-free Survival (DFS) | 14.2 months |
Comparison: Assuming a median DFS time of 15 months (Arm 2), hypothesized increase in DFS corresponding to median DFS time of 25 months (Arm 1). Assuming an exponential distribution and constant hazards, 183 HER2-positive participants accrued over 5 years and followed for 3 years would result in 162 disease-free survival events and provide 90% statistical power to detect this difference with a 2-sided α of 0.05 and 2 interim analyses. See Limitations and Caveats section.p-value: 0.8595% CI: [0.69, 1.36]Log Rank
Secondary
Frequency of Highest Grade Adverse Event Per Participant
Common Terminology Criteria for Adverse Events (version 4.0 before 4-1-2018; then version 5.0) grades adverse event severity from 1=mild to 5=death. Summary data provided is in this outcome measure; see Adverse Events Module for specific adverse event data.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.
Population: Eligible participants who started study treatment
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Chemoradiation and Trastuzumab (Arm 1) | Frequency of Highest Grade Adverse Event Per Participant | All Adverse Events | Grade 3 | 49 Participants |
| Chemoradiation and Trastuzumab (Arm 1) | Frequency of Highest Grade Adverse Event Per Participant | Reported as Definitely, Probably, or Possibly Related to Protocol Treatment | Grade 1 | 2 Participants |
| Chemoradiation and Trastuzumab (Arm 1) | Frequency of Highest Grade Adverse Event Per Participant | All Adverse Events | Grade 2 | 14 Participants |
| Chemoradiation and Trastuzumab (Arm 1) | Frequency of Highest Grade Adverse Event Per Participant | Reported as Definitely, Probably, or Possibly Related to Protocol Treatment | Grade 2 | 27 Participants |
| Chemoradiation and Trastuzumab (Arm 1) | Frequency of Highest Grade Adverse Event Per Participant | All Adverse Events | Grade 4 | 27 Participants |
| Chemoradiation and Trastuzumab (Arm 1) | Frequency of Highest Grade Adverse Event Per Participant | All Adverse Events | Grade 1 | 0 Participants |
| Chemoradiation and Trastuzumab (Arm 1) | Frequency of Highest Grade Adverse Event Per Participant | Reported as Definitely, Probably, or Possibly Related to Protocol Treatment | Grade 4 | 20 Participants |
| Chemoradiation and Trastuzumab (Arm 1) | Frequency of Highest Grade Adverse Event Per Participant | All Adverse Events | Grade 5 | 5 Participants |
| Chemoradiation and Trastuzumab (Arm 1) | Frequency of Highest Grade Adverse Event Per Participant | Reported as Definitely, Probably, or Possibly Related to Protocol Treatment | Grade 5 | 5 Participants |
| Chemoradiation and Trastuzumab (Arm 1) | Frequency of Highest Grade Adverse Event Per Participant | Reported as Definitely, Probably, or Possibly Related to Protocol Treatment | Grade 3 | 41 Participants |
| Chemoradiation (Arm 2) | Frequency of Highest Grade Adverse Event Per Participant | Reported as Definitely, Probably, or Possibly Related to Protocol Treatment | Grade 5 | 3 Participants |
| Chemoradiation (Arm 2) | Frequency of Highest Grade Adverse Event Per Participant | All Adverse Events | Grade 1 | 0 Participants |
| Chemoradiation (Arm 2) | Frequency of Highest Grade Adverse Event Per Participant | All Adverse Events | Grade 2 | 12 Participants |
| Chemoradiation (Arm 2) | Frequency of Highest Grade Adverse Event Per Participant | All Adverse Events | Grade 3 | 56 Participants |
| Chemoradiation (Arm 2) | Frequency of Highest Grade Adverse Event Per Participant | All Adverse Events | Grade 4 | 25 Participants |
| Chemoradiation (Arm 2) | Frequency of Highest Grade Adverse Event Per Participant | All Adverse Events | Grade 5 | 3 Participants |
| Chemoradiation (Arm 2) | Frequency of Highest Grade Adverse Event Per Participant | Reported as Definitely, Probably, or Possibly Related to Protocol Treatment | Grade 1 | 0 Participants |
| Chemoradiation (Arm 2) | Frequency of Highest Grade Adverse Event Per Participant | Reported as Definitely, Probably, or Possibly Related to Protocol Treatment | Grade 2 | 20 Participants |
| Chemoradiation (Arm 2) | Frequency of Highest Grade Adverse Event Per Participant | Reported as Definitely, Probably, or Possibly Related to Protocol Treatment | Grade 3 | 52 Participants |
| Chemoradiation (Arm 2) | Frequency of Highest Grade Adverse Event Per Participant | Reported as Definitely, Probably, or Possibly Related to Protocol Treatment | Grade 4 | 21 Participants |
Secondary
Molecular Correlates of Efficacy
Time frame: From randomization to last follow-up. Maximum follow-up at time of primary outcome measure analysis was 8 years.
Population: The protocol did not provide sufficient detail to meet current National Cancer Institute requirements for release of specimens from the NRG tissue bank for the protocol-specified analysis, therefore no assays were performed, and no data were collected for this outcome measure. Specimen use will require federal approval and funding separate from this trial.
Secondary
Number of Participants With Any Cardiac Adverse Events Regardless of Attribution
Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event (AE) severity from 1=mild to 5=death. Logistic regression was used to evaluate treatment arm, clinical tumor stage (T stage), Zubrod Performance Status, gender, presence of adenopathy, and age as possible predictors of cardiac adverse events. Results of the final model are reported in the statistical analysis section. Summary adverse event data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.
Population: Eligible participants who started study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemoradiation and Trastuzumab (Arm 1) | Number of Participants With Any Cardiac Adverse Events Regardless of Attribution | 30 Participants |
| Chemoradiation (Arm 2) | Number of Participants With Any Cardiac Adverse Events Regardless of Attribution | 24 Participants |
Comparison: Logistic regression was used to model the association of treatment arm (Arm 1 vs. 2 \[reference level(RL)\]), T stage (T3 vs.T1,T2 \[RL\]), Zubrod (1,2 vs. 0 \[RL\]), gender (male vs. female \[RL\]), presence of adenopathy (yes vs. no \[RL\]), and age (≥ 60 vs. \<60 \[RL\]) with the occurrence of any cardiac AE, using backwards step-wise model selection requiring p≤0.05 for a covariate to remain in the model. Final model covariates are reported. Age is reported here. No other covariates reported.p-value: 0.02195% CI: [1.13, 4.86]Regression, Logistic
Secondary
Overall Survival
Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis occurred after 109 deaths were reported.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.
Population: Eligible randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemoradiation and Trastuzumab (Arm 1) | Overall Survival | 38.5 months |
| Chemoradiation (Arm 2) | Overall Survival | 38.9 months |
p-value: 0.9595% CI: [0.69, 1.47]Log Rank
Secondary
Percentage of Participants With Pathologic Complete Response at Surgery
Pathologic Complete Response (pCR) is evaluated after surgery and is based on the pathology review of the submitted surgical specimen. Pathologic Complete Response occurs if the pathologist determines that the resected esophageal specimen, accompanying lymph nodes, and surgical margins are all free of tumor.
Time frame: At the time of surgery, 5-8 weeks after completion of radiation therapy.
Population: Eligible participants who had surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemoradiation and Trastuzumab (Arm 1) | Percentage of Participants With Pathologic Complete Response at Surgery | 27 percentage of participants |
| Chemoradiation (Arm 2) | Percentage of Participants With Pathologic Complete Response at Surgery | 29 percentage of participants |
p-value: 0.71Chi-squared
Secondary
Percentage of Patients With Improvement in the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) Esophageal Cancer Subscale (ECS) Subscale After Treatment
The ECS is a 17-item self-report instrument designed to measure multidimensional quality of life in patients with esophagus cancer with a total score ranging from 0-68. It is to be administered with the Functional Assessment of Cancer Therapy - General (FACT-G). A higher score indicates better QOL. Improvement is defined as an increase from the baseline score of at least 5 points.
Time frame: Baseline, 6-8 weeks after end of radiation therapy (approximately 11.5-13.5 weeks from treatment start), 1 and 2 years from treatment start
Population: Eligible participants who consented to quality of life evaluation and who had baseline and time point data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chemoradiation and Trastuzumab (Arm 1) | Percentage of Patients With Improvement in the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) Esophageal Cancer Subscale (ECS) Subscale After Treatment | 6-8 weeks from end of treatment | 46 percentage of participants |
| Chemoradiation and Trastuzumab (Arm 1) | Percentage of Patients With Improvement in the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) Esophageal Cancer Subscale (ECS) Subscale After Treatment | 1 year from start of treatment | 39 percentage of participants |
| Chemoradiation and Trastuzumab (Arm 1) | Percentage of Patients With Improvement in the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) Esophageal Cancer Subscale (ECS) Subscale After Treatment | 2 years from start of treatment | 41 percentage of participants |
| Chemoradiation (Arm 2) | Percentage of Patients With Improvement in the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) Esophageal Cancer Subscale (ECS) Subscale After Treatment | 6-8 weeks from end of treatment | 38 percentage of participants |
| Chemoradiation (Arm 2) | Percentage of Patients With Improvement in the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) Esophageal Cancer Subscale (ECS) Subscale After Treatment | 1 year from start of treatment | 42 percentage of participants |
| Chemoradiation (Arm 2) | Percentage of Patients With Improvement in the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) Esophageal Cancer Subscale (ECS) Subscale After Treatment | 2 years from start of treatment | 27 percentage of participants |
Comparison: 6-8 weeksp-value: 0.39Chi-squared
Comparison: 1 yearp-value: 0.78Chi-squared
Comparison: 2 yearsp-value: 0.28Chi-squared
Secondary
Quality-adjusted Survival
Time frame: From randomization to last follow-up. Maximum follow-up at time of primary outcome measure analysis was 8 years.
Population: The protocol states that this outcome measure will be analyzed only if primary outcome results are positive, i.e. support the primary hypothesis of this study. Therefore no participants were analyzed for this outcome measure.