Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Conditions
Brief summary
This study will evaluate the efficacy and safety of atezolizumab compared with placebo as adjuvant therapy after definitive local therapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Interventions
DRUGAtezolizumab
Atezolizumab intravenous infusion will be administered at a fixed dose on Day 1 of each 21-day cycle for 16 cycles.
DRUGPlacebo
Placebo intravenous infusion will be administered a fixed dose on Day 1 of each 21-day cycle for 16 cycles.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) * Human Papilloma Virus (HPV) status * Completed definitive local therapy * Absence of metastatic disease as documented by radiographic scans * Adequate hematologic and end-organ function * For patients receiving therapeutic anticoagulation: stable anticoagulant regimen * For women of childbearing potential: agreement to remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for 5 months after the last dose of study treatment. Women must refrain from donating eggs during this same period. * Confirmed response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) to definitive local therapy documented by CT with contrast or MRI with contract to head and neck region done \>= 8 weeks after completion of definitive local therapy and within 28 days prior to initiation of study drug.
Exclusion criteria
* Patients who have received surgery alone or radiotherapy alone as definitive local therapy * Squamous cell carcinoma of the nasopharynx or paranasal sinuses or non-squamous histology * Evidence of disease progression or metastatic disease during or following definitive local therapy documented in post-definitive local therapy screening scans * Uncontrolled or symptomatic hypercalcemia * Active or history of autoimmune disease or immune deficiency * Active tuberculosis * Significant cardiovascular disease * History of malignancy, including prior SCCHN primary tumors within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death * Prior allogeneic stem cell or solid organ transplantation * Current treatment with anti-viral therapy for Hepatitis B Virus (HBV) * Treatment with systemic immunostimulatory agents * Treatment with systemic immunosuppressive medication * History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins * Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the last dose of study treatment * Patients who have received a non-FDA or non-EMA approved anti-EGFR agent or any other non-FDA or non-EMA, approved agent as part of definitive local therapy, unless the unapproved agent was given in addition to an approved agent * Any systemic therapies after permitted definitive local therapies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Investigator-Assessed Event-Free Survival (INV-assessed EFS) | Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years) | EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression \[per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)\] per assessment by investigator, or death from any cause, whichever occurred first. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. EFS was estimated using the Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Independent Review Facility (IRF) Assessed EFS | Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years) | EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by IRF, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. EFS was estimated using the Kaplan-Meier method. |
| Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years | From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years | EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by IRF, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. Kaplan-Meier approach was used to estimate percentage of participants who were event-free for EFS at 1, 2, 3 & 4 years. |
| Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years | From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years | EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by the investigator, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. Kaplan-Meier approach was used to estimate percentage of participants who were event-free for EFS at 1, 2, 3 & 4 years. |
| Percentage of Participants Event-Free for OS at 2, 3, and 5 Years | From randomization to OS event or date last known to be alive at 2, 3, and 5 Years | OS was defined as the time from randomization to death from any cause. Data from participants who were alive at the time of the analysis was censored as of the last date they were known to be alive. Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for OS at 2, 3 and 5 years. |
| Overall Survival (OS) | Randomization to death from any cause (up to 5 years, 5 months) | OS was defined as the time from randomization to death from any cause. Data from participants who were alive at the time of the analysis was censored as of the last date they were known to be alive. OS was estimated using the Kaplan-Meier method. |
| Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Baseline, Day 1 of Cycles 2 to 16 (Cycle length = 21 days); study discontinuation visit (up to 1 year); Follow-up approximately every 3 months until disease recurrence or progression (up to approximately 4.5 years) | EORTC QLQ-C30 scale consists of 30 questions that assess participant functioning (physical, emotional, role, cognitive, and social), symptom (fatigue, nausea and vomiting, pain), global health/quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Change in HRQoL was assessed using participant responses to questions regarding Global Health Status (Question 29: GHS; How would you rate your overall health during the past week?) and QoL (Question 30: QoL; How would you rate your overall quality of life during the past week?) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized. Scores range from 0-100. A higher score indicates a better outcome. |
| Number of Participants With at Least One Adverse Event (AE) | From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months) | An AE is untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. |
| Serum Concentration of Atezolizumab | Predose and 0.5 hours post dose on Cycle 1 Day 1; Predose on Day 1 of Cycles 2, 4, 8, and 16 (Cycle length=21 days); study discontinuation visit (up to 1 year) | — |
| Number of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab | Predose on Day 1 of Cycles 1, 2, 4, 8 and 16 (Cycle length=21 days) | Number of participants positive for Treatment Emergent ADA is the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during the study period. |
| Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Baseline, Day 1 of Cycles 2 to 16 (Cycle length = 21 days); study discontinuation visit (up to 1 year); Follow-up approximately every 3 months until disease recurrence or progression (up to approximately 4.5 years) | EORTC QLQ-C30 scale consists of 30 questions that assess participant functioning (physical, emotional, role, cognitive, and social), symptoms (fatigue, nausea and vomiting, pain), global health/quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Change in PF was assessed using the PF scale, where participant responses to 5 questions about daily activities (strenuous activities, long walks, short walks, bed/chair rest & needing help with eating, dressing, washing themselves, or using the toilet) was scored on a 4-point scale (1=Not at All to 4=Very Much). Scores were linearly transformed on a scale of 0 to 100, with a high score indicating worst functioning. |
Countries
Australia, Belgium, Brazil, Canada, China, France, Germany, Hungary, India, Italy, Japan, Poland, Portugal, Russia, South Africa, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study across 128 investigative sites in 23 countries from 03 April 2018 to 06 March 2024.
Pre-assignment details
A total of 406 participants with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were randomized in 1:1 ratio to receive either atezolizumab or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received atezolizumab matching placebo, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first. | 203 |
| Atezolizumab Participants received atezolizumab 1200 mg, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first. | 203 |
| Total | 406 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 67 | 70 |
| Overall Study | Lost to Follow-up | 4 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Study Terminated by Sponsor | 120 | 121 |
| Overall Study | Withdrawal by Subject | 12 | 9 |
Baseline characteristics
| Characteristic | Atezolizumab | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 59.4 years STANDARD_DEVIATION 8.5 | 58.5 years STANDARD_DEVIATION 9.4 | 57.7 years STANDARD_DEVIATION 10.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 24 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 183 Participants | 364 Participants | 181 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants | 18 Participants | 9 Participants |
| Human papilloma virus (HPV) Status Negative | 168 Participants | 334 Participants | 166 Participants |
| Human papilloma virus (HPV) Status Positive | 35 Participants | 72 Participants | 37 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 68 Participants | 129 Participants | 61 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 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 | 12 Participants | 18 Participants | 6 Participants |
| Race (NIH/OMB) White | 121 Participants | 256 Participants | 135 Participants |
| Response to Definitive Local Therapy Complete Response (CR) | 170 Participants | 340 Participants | 170 Participants |
| Response to Definitive Local Therapy Partial Response (PR) or Stable Disease (SD) | 33 Participants | 66 Participants | 33 Participants |
| Sex: Female, Male Female | 35 Participants | 64 Participants | 29 Participants |
| Sex: Female, Male Male | 168 Participants | 342 Participants | 174 Participants |
| Type of Definitive Local Therapy No Primary Surgery | 124 Participants | 249 Participants | 125 Participants |
| Type of Definitive Local Therapy Primary Surgery | 79 Participants | 157 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 69 / 203 | 70 / 202 |
| other Total, other adverse events | 144 / 203 | 155 / 202 |
| serious Total, serious adverse events | 32 / 203 | 32 / 202 |
Outcome results
Primary
Investigator-Assessed Event-Free Survival (INV-assessed EFS)
EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression \[per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)\] per assessment by investigator, or death from any cause, whichever occurred first. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. EFS was estimated using the Kaplan-Meier method.
Time frame: Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years)
Population: ITT population included all randomized participants, regardless of whether they received any of the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Investigator-Assessed Event-Free Survival (INV-assessed EFS) | 52.73 months |
| Atezolizumab | Investigator-Assessed Event-Free Survival (INV-assessed EFS) | 59.47 months |
Comparison: Stratified Analysis: The stratification factors were response to definitive local therapy, human papillomavirus (HPV) status and type of definitive local therapy as per interactive voice or web-based response system (IxRS).p-value: 0.680495% CI: [0.7, 1.26]Log Rank
Secondary
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score
EORTC QLQ-C30 scale consists of 30 questions that assess participant functioning (physical, emotional, role, cognitive, and social), symptom (fatigue, nausea and vomiting, pain), global health/quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Change in HRQoL was assessed using participant responses to questions regarding Global Health Status (Question 29: GHS; How would you rate your overall health during the past week?) and QoL (Question 30: QoL; How would you rate your overall quality of life during the past week?) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized. Scores range from 0-100. A higher score indicates a better outcome.
Time frame: Baseline, Day 1 of Cycles 2 to 16 (Cycle length = 21 days); study discontinuation visit (up to 1 year); Follow-up approximately every 3 months until disease recurrence or progression (up to approximately 4.5 years)
Population: ITT population included all randomized participants, regardless of whether they received any of the assigned treatment. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 10 Day 1 | 7.83 score on a scale | Standard Deviation 22.29 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 2 | 4.67 score on a scale | Standard Deviation 21.33 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 6 Day 1 | 4.66 score on a scale | Standard Deviation 23.81 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 3 | -1.77 score on a scale | Standard Deviation 18.84 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 11 Day 1 | 7.65 score on a scale | Standard Deviation 21.21 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 4 | 0.74 score on a scale | Standard Deviation 25.32 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 4 Day 1 | 6.05 score on a scale | Standard Deviation 21.04 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 5 | 3.16 score on a scale | Standard Deviation 23.19 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 12 Day 1 | 7.47 score on a scale | Standard Deviation 22.52 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 6 | 6.32 score on a scale | Standard Deviation 23.11 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 7 Day 1 | 7.25 score on a scale | Standard Deviation 21.71 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 7 | 2.45 score on a scale | Standard Deviation 23.34 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 13 Day 1 | 8.45 score on a scale | Standard Deviation 21.37 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 8 | -8.33 score on a scale | Standard Deviation 32 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 3 Day 1 | 4.87 score on a scale | Standard Deviation 24.02 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 9 | 3.70 score on a scale | Standard Deviation 17.24 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 14 Day 1 | 6.91 score on a scale | Standard Deviation 21.82 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 10 | -15.00 score on a scale | Standard Deviation 50.14 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 8 Day 1 | 7.58 score on a scale | Standard Deviation 21.48 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 11 | -4.63 score on a scale | Standard Deviation 50.88 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 15 Day 1 | 7.21 score on a scale | Standard Deviation 21.58 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 12 | 20.00 score on a scale | Standard Deviation 40.23 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Baseline (Cycle 1 Day 1) | 66.92 score on a scale | Standard Deviation 21.41 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 13 | 11.11 score on a scale | Standard Deviation 38.61 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 5 Day 1 | 5.29 score on a scale | Standard Deviation 22.8 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 14 | 8.33 score on a scale | Standard Deviation 11.79 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 16 Day 1 | 6.30 score on a scale | Standard Deviation 22.87 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 15 | 14.58 score on a scale | Standard Deviation 34.94 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 16 | 2.78 score on a scale | Standard Deviation 12.73 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 17 | -8.33 score on a scale | Standard Deviation 11.79 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 18 | 8.33 score on a scale | Standard Deviation 11.79 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 9 Day 1 | 6.30 score on a scale | Standard Deviation 23.2 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Study Discontinuation | 3.86 score on a scale | Standard Deviation 23.64 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 2 Day 1 | 2.99 score on a scale | Standard Deviation 20.32 |
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 1 | 1.50 score on a scale | Standard Deviation 25.01 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 12 | -14.58 score on a scale | Standard Deviation 20.83 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Baseline (Cycle 1 Day 1) | 67.54 score on a scale | Standard Deviation 20.79 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 2 Day 1 | 0.09 score on a scale | Standard Deviation 18.33 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 3 Day 1 | 0.49 score on a scale | Standard Deviation 17.35 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 4 Day 1 | 1.34 score on a scale | Standard Deviation 17.33 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 5 Day 1 | 1.19 score on a scale | Standard Deviation 18.25 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 6 Day 1 | 3.17 score on a scale | Standard Deviation 18.01 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 7 Day 1 | 4.09 score on a scale | Standard Deviation 17.47 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 8 Day 1 | 4.25 score on a scale | Standard Deviation 19.93 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 9 Day 1 | 3.00 score on a scale | Standard Deviation 17.93 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 10 Day 1 | 3.85 score on a scale | Standard Deviation 17.12 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 11 Day 1 | 2.64 score on a scale | Standard Deviation 17.35 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 12 Day 1 | 2.60 score on a scale | Standard Deviation 17.75 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 13 Day 1 | 2.94 score on a scale | Standard Deviation 18.41 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 14 Day 1 | 3.39 score on a scale | Standard Deviation 17.04 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 15 Day 1 | 5.27 score on a scale | Standard Deviation 18.13 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Cycle 16 Day 1 | 6.05 score on a scale | Standard Deviation 17.83 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Study Discontinuation | 1.55 score on a scale | Standard Deviation 18.41 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 1 | -5.83 score on a scale | Standard Deviation 25.32 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 2 | -0.95 score on a scale | Standard Deviation 21.73 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 3 | 2.53 score on a scale | Standard Deviation 18.57 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 4 | 3.87 score on a scale | Standard Deviation 22.51 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 5 | 4.76 score on a scale | Standard Deviation 23.36 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 6 | 1.85 score on a scale | Standard Deviation 17.28 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 7 | -10.26 score on a scale | Standard Deviation 23.11 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 8 | 2.27 score on a scale | Standard Deviation 11.84 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 9 | -1.85 score on a scale | Standard Deviation 12.34 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 10 | 9.38 score on a scale | Standard Deviation 9.38 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 11 | -4.17 score on a scale | Standard Deviation 19.84 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 13 | -2.78 score on a scale | Standard Deviation 12.73 |
| Atezolizumab | Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score | Change at Follow Up 14 | -16.67 score on a scale | Standard Deviation 0 |
Secondary
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score
EORTC QLQ-C30 scale consists of 30 questions that assess participant functioning (physical, emotional, role, cognitive, and social), symptoms (fatigue, nausea and vomiting, pain), global health/quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Change in PF was assessed using the PF scale, where participant responses to 5 questions about daily activities (strenuous activities, long walks, short walks, bed/chair rest & needing help with eating, dressing, washing themselves, or using the toilet) was scored on a 4-point scale (1=Not at All to 4=Very Much). Scores were linearly transformed on a scale of 0 to 100, with a high score indicating worst functioning.
Time frame: Baseline, Day 1 of Cycles 2 to 16 (Cycle length = 21 days); study discontinuation visit (up to 1 year); Follow-up approximately every 3 months until disease recurrence or progression (up to approximately 4.5 years)
Population: ITT population included all randomized participants, regardless of whether they received any of the assigned treatment. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 10 Day 1 | 4.41 score on a scale | Standard Deviation 14.3 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 2 | -1.15 score on a scale | Standard Deviation 18.1 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 6 Day 1 | 4.03 score on a scale | Standard Deviation 12.76 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 3 | -0.81 score on a scale | Standard Deviation 17.17 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 11 Day 1 | 3.82 score on a scale | Standard Deviation 14.2 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 4 | -1.90 score on a scale | Standard Deviation 18.62 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 4 Day 1 | 2.90 score on a scale | Standard Deviation 13 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 5 | -2.00 score on a scale | Standard Deviation 26.21 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 12 Day 1 | 4.35 score on a scale | Standard Deviation 15.23 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 6 | -3.61 score on a scale | Standard Deviation 18.08 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 7 Day 1 | 4.33 score on a scale | Standard Deviation 13.07 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 7 | -6.75 score on a scale | Standard Deviation 21.85 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 13 Day 1 | 5.62 score on a scale | Standard Deviation 13.63 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 8 | -13.08 score on a scale | Standard Deviation 28.96 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 3 Day 1 | 3.75 score on a scale | Standard Deviation 12.03 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 9 | 2.88 score on a scale | Standard Deviation 14.38 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 14 Day 1 | 6.73 score on a scale | Standard Deviation 13.67 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 10 | -16.43 score on a scale | Standard Deviation 32.5 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 8 Day 1 | 4.63 score on a scale | Standard Deviation 13.07 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 11 | -10.00 score on a scale | Standard Deviation 35.31 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 15 Day 1 | 6.13 score on a scale | Standard Deviation 13.11 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 12 | -6.67 score on a scale | Standard Deviation 8.43 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Baseline (Cycle 1 Day 1) | 82.78 score on a scale | Standard Deviation 16.36 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 13 | -5.71 score on a scale | Standard Deviation 7.13 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 5 Day 1 | 4.69 score on a scale | Standard Deviation 13.86 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 14 | -17.78 score on a scale | Standard Deviation 42.86 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 16 Day 1 | 5.92 score on a scale | Standard Deviation 14.85 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 15 | -5.00 score on a scale | Standard Deviation 6.38 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 16 | 2.22 score on a scale | Standard Deviation 10.18 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 17 | -3.33 score on a scale | Standard Deviation 4.71 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 18 | 13.33 score on a scale | Standard Deviation 0 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 9 Day 1 | 4.62 score on a scale | Standard Deviation 13.86 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Study Discontinuation | 2.94 score on a scale | Standard Deviation 16.52 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 2 Day 1 | 2.40 score on a scale | Standard Deviation 11.09 |
| Placebo | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 1 | 1.47 score on a scale | Standard Deviation 16.36 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 12 | 0.00 score on a scale | Standard Deviation 14.4 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Baseline (Cycle 1 Day 1) | 83.46 score on a scale | Standard Deviation 16.79 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 2 Day 1 | -0.58 score on a scale | Standard Deviation 10.54 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 3 Day 1 | -0.13 score on a scale | Standard Deviation 12.62 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 4 Day 1 | 0.77 score on a scale | Standard Deviation 13.42 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 5 Day 1 | 1.60 score on a scale | Standard Deviation 12.15 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 6 Day 1 | 2.18 score on a scale | Standard Deviation 13.87 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 7 Day 1 | 3.56 score on a scale | Standard Deviation 13.68 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 8 Day 1 | 3.19 score on a scale | Standard Deviation 13.71 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 9 Day 1 | 2.96 score on a scale | Standard Deviation 14.41 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 10 Day 1 | 2.12 score on a scale | Standard Deviation 14.22 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 11 Day 1 | 3.69 score on a scale | Standard Deviation 12.43 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 12 Day 1 | 3.05 score on a scale | Standard Deviation 14.89 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 13 Day 1 | 3.30 score on a scale | Standard Deviation 15.02 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 14 Day 1 | 3.20 score on a scale | Standard Deviation 13.36 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 15 Day 1 | 3.99 score on a scale | Standard Deviation 12.92 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Cycle 16 Day 1 | 4.11 score on a scale | Standard Deviation 12.88 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Study Discontinuation | 2.70 score on a scale | Standard Deviation 14.2 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 1 | -6.63 score on a scale | Standard Deviation 24.41 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 2 | 0.19 score on a scale | Standard Deviation 17.34 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 3 | 2.68 score on a scale | Standard Deviation 18.75 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 4 | -2.56 score on a scale | Standard Deviation 28.57 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 5 | -6.03 score on a scale | Standard Deviation 35.58 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 6 | -3.24 score on a scale | Standard Deviation 23.84 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 7 | 1.54 score on a scale | Standard Deviation 24.82 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 8 | 1.36 score on a scale | Standard Deviation 33.11 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 9 | 4.63 score on a scale | Standard Deviation 17.36 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 10 | 3.33 score on a scale | Standard Deviation 13.8 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 11 | -16.67 score on a scale | Standard Deviation 24.65 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 13 | 4.44 score on a scale | Standard Deviation 10.18 |
| Atezolizumab | Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score | Change at Follow Up 14 | -6.67 score on a scale | Standard Deviation 0 |
Secondary
Independent Review Facility (IRF) Assessed EFS
EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by IRF, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. EFS was estimated using the Kaplan-Meier method.
Time frame: Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years)
Population: ITT population included all randomized participants, regardless of whether they received any of the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Independent Review Facility (IRF) Assessed EFS | 52.73 months |
| Atezolizumab | Independent Review Facility (IRF) Assessed EFS | 59.47 months |
Comparison: Stratified Analysis: The stratification factors were response to definitive local therapy, HPV status and type of definitive local therapy as per interactive voice or web-based response system (IxRS).p-value: 0.911595% CI: [0.73, 1.32]Log Rank
Secondary
Number of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab
Number of participants positive for Treatment Emergent ADA is the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during the study period.
Time frame: Predose on Day 1 of Cycles 1, 2, 4, 8 and 16 (Cycle length=21 days)
Population: ADA evaluable population included all randomized participants who received at least one dose of atezolizumab and who had at least one post-baseline ADA result.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab | 13 Participants |
Secondary
Number of Participants With at Least One Adverse Event (AE)
An AE is untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product.
Time frame: From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months)
Population: Safety evaluable population included all randomized participants who received any amount of the study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With at Least One Adverse Event (AE) | 186 Participants |
| Atezolizumab | Number of Participants With at Least One Adverse Event (AE) | 192 Participants |
Secondary
Overall Survival (OS)
OS was defined as the time from randomization to death from any cause. Data from participants who were alive at the time of the analysis was censored as of the last date they were known to be alive. OS was estimated using the Kaplan-Meier method.
Time frame: Randomization to death from any cause (up to 5 years, 5 months)
Population: ITT population included all randomized participants, regardless of whether they received any of the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Overall Survival (OS) | NA months |
| Atezolizumab | Overall Survival (OS) | NA months |
Comparison: Stratified Analysis: The stratification factors were response to definitive local therapy, HPV status and type of definitive local therapy as per interactive voice or web-based response system (IxRS).p-value: 0.837195% CI: [0.68, 1.36]Log Rank
Secondary
Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years
EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by the investigator, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. Kaplan-Meier approach was used to estimate percentage of participants who were event-free for EFS at 1, 2, 3 & 4 years.
Time frame: From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years
Population: ITT population included all randomized participants, regardless of whether they received any of the assigned treatment. Number analyzed per timepoint are unique number of participants out of all the assessed participants who remain at risk for an EFS event at that timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years | 1 Year | 70.84 percentage of participants |
| Placebo | Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years | 2 Year | 63.81 percentage of participants |
| Placebo | Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years | 3 Year | 58.57 percentage of participants |
| Placebo | Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years | 4 Year | 55.51 percentage of participants |
| Atezolizumab | Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years | 4 Year | 56.82 percentage of participants |
| Atezolizumab | Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years | 1 Year | 76.01 percentage of participants |
| Atezolizumab | Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years | 3 Year | 61.71 percentage of participants |
| Atezolizumab | Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years | 2 Year | 67.41 percentage of participants |
Comparison: Difference in EFS Event-Free Rates at 1 yearp-value: 0.239395% CI: [-3.44, 13.79]Z test
Comparison: Difference in EFS Event-Free Rates at 2 yearsp-value: 0.447295% CI: [-5.69, 12.9]Z test
Comparison: Difference in EFS Event-Free Rates at 3 yearsp-value: 0.522295% CI: [-6.49, 12.77]Z test
Comparison: Difference in EFS Event-Free Rates at 4 yearsp-value: 0.796795% CI: [-8.64, 11.26]Z test
Secondary
Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years
EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by IRF, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. Kaplan-Meier approach was used to estimate percentage of participants who were event-free for EFS at 1, 2, 3 & 4 years.
Time frame: From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years
Population: ITT population included all randomized participants, regardless of whether they received any of the assigned treatment. Number analyzed per timepoint are unique number of participants out of all the assessed participants who remain at risk for an EFS event at that timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years | 1 Year | 72.59 percentage of participants |
| Placebo | Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years | 2 Year | 65.85 percentage of participants |
| Placebo | Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years | 3 Year | 59.87 percentage of participants |
| Placebo | Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years | 4 Year | 54.71 percentage of participants |
| Atezolizumab | Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years | 4 Year | 54.72 percentage of participants |
| Atezolizumab | Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years | 1 Year | 71.92 percentage of participants |
| Atezolizumab | Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years | 3 Year | 61.07 percentage of participants |
| Atezolizumab | Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years | 2 Year | 66.31 percentage of participants |
Comparison: Difference in EFS Event-Free Rates at 1 yearp-value: 0.881695% CI: [-9.45, 8.11]Z test
Comparison: Difference in EFS Event-Free Rates at 2 yearsp-value: 0.923495% CI: [-8.86, 9.78]Z test
Comparison: Difference in EFS Event-Free Rates at 3 yearsp-value: 0.80995% CI: [-8.49, 10.88]Z test
Comparison: Difference in EFS Event-Free Rates at 4 yearsp-value: 0.998595% CI: [-10.17, 10.19]Z test
Secondary
Percentage of Participants Event-Free for OS at 2, 3, and 5 Years
OS was defined as the time from randomization to death from any cause. Data from participants who were alive at the time of the analysis was censored as of the last date they were known to be alive. Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for OS at 2, 3 and 5 years.
Time frame: From randomization to OS event or date last known to be alive at 2, 3, and 5 Years
Population: ITT population included all randomized participants, regardless of whether they received any of the assigned treatment. Number analyzed per timepoint are unique number of participants out of all the assessed participants who remain at risk for an OS event at that timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Event-Free for OS at 2, 3, and 5 Years | 2 Year | 79.23 percentage of participants |
| Placebo | Percentage of Participants Event-Free for OS at 2, 3, and 5 Years | 3 Year | 73.59 percentage of participants |
| Placebo | Percentage of Participants Event-Free for OS at 2, 3, and 5 Years | 5 Year | 62.00 percentage of participants |
| Atezolizumab | Percentage of Participants Event-Free for OS at 2, 3, and 5 Years | 2 Year | 82.00 percentage of participants |
| Atezolizumab | Percentage of Participants Event-Free for OS at 2, 3, and 5 Years | 3 Year | 72.34 percentage of participants |
| Atezolizumab | Percentage of Participants Event-Free for OS at 2, 3, and 5 Years | 5 Year | 60.93 percentage of participants |
Comparison: Difference in OS Event-Free Rates at 2 yearsp-value: 0.481995% CI: [-4.95, 10.49]Z test
Comparison: Difference in OS Event-Free Rates at 3 yearsp-value: 0.778395% CI: [-9.97, 7.47]Z test
Comparison: Difference in OS Event-Free Rates at 5 yearsp-value: 0.892495% CI: [-16.56, 14.42]Z test
Secondary
Serum Concentration of Atezolizumab
Time frame: Predose and 0.5 hours post dose on Cycle 1 Day 1; Predose on Day 1 of Cycles 2, 4, 8, and 16 (Cycle length=21 days); study discontinuation visit (up to 1 year)
Population: Pharmacokinetic (PK)-evaluable population included all participants who received at least one dose of atezolizumab and provided at least one PK sample that was evaluable. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at specified timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Concentration of Atezolizumab | Cycle 8 Day 1: Predose | 238 micrograms per milliliters (ug/mL) | Geometric Coefficient of Variation 40.6 |
| Placebo | Serum Concentration of Atezolizumab | Cycle 16 Day 1: Predose | 257 micrograms per milliliters (ug/mL) | Geometric Coefficient of Variation 40.3 |
| Placebo | Serum Concentration of Atezolizumab | Cycle 1 Day 1: Predose | NA micrograms per milliliters (ug/mL) | — |
| Placebo | Serum Concentration of Atezolizumab | Cycle 1 Day 1: 0.5 hours Post-dose | 447 micrograms per milliliters (ug/mL) | Geometric Coefficient of Variation 27.1 |
| Placebo | Serum Concentration of Atezolizumab | Cycle 2 Day 1: Predose | 99.2 micrograms per milliliters (ug/mL) | Geometric Coefficient of Variation 31.1 |
| Placebo | Serum Concentration of Atezolizumab | Cycle 4 Day 1: Predose | 186 micrograms per milliliters (ug/mL) | Geometric Coefficient of Variation 64.3 |
| Placebo | Serum Concentration of Atezolizumab | Study Discontinuation | 178 micrograms per milliliters (ug/mL) | Geometric Coefficient of Variation 141 |