Gastric Cancer Third Line, Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Conditions
Keywords
Avelumab, Gastric cancer, Gastroesophageal junction adenocarcinoma
Brief summary
The purpose of this study was to demonstrate superiority of treatment with avelumab plus best supportive care (BSC) versus physician's choice (chosen from a pre-specified list of therapeutic options) plus BSC.
Interventions
DRUGAvelumab
Avelumab was administered as a 1-hour intravenous (IV) infusion at 10 milligram per kilogram (mg/kg) once every 2-week treatment cycle until confirmed progressive disease or unacceptable toxicity along with best supportive care (BSC).
DRUGIrinotecan
Irinotecan was administered at a dose of 150 mg/m \^2 on Day 1 and 15 of a 4-week treatment cycle until disease progression or unacceptable toxicities along with BSC.
DRUGPaclitaxel
Paclitaxel was administered at a dose of 80 mg/m\^2 on Day 1, 8, and 15 of a 4-week treatment cycle until disease progression or unacceptable toxicities along with BSC.
OTHERBest Supportive Care (BSC)
BSC is defined as treatment administered with the intent to maximize Quality of life without a specific antineoplastic regimen and is based on investigator's discretion. BSC was administered once every 3 weeks.
Sponsors
Merck KGaA, Darmstadt, Germany
EMD Serono Research & Development Institute, Inc.
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
* Male or female subjects aged greater than or equal to (\>=) 18 years * Subjects with histologically confirmed recurrent unresectable, recurrent locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction (GEJ) * Availability of a formalin-fixed, paraffin-embedded (FFPE) block containing tumor tissue * Subjects must have received 2 prior courses of systemic treatment for unresectable, recurrent, locally advanced or metastatic gastric cancer, and must have progressed after the second line * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 at trial entry * Adequate hematological, hepatic and renal functions defined by the protocol * Negative blood pregnancy test at Screening for women of childbearing potential. * Highly effective contraception for both male and female subjects if the risk of conception exists Other protocol defined inclusion criteria could apply
Exclusion criteria
* Prior therapy with any antibody or drug targeting T-cell coregulatory proteins * Concurrent anticancer treatment * Major surgery * Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to less than \[\<\] 10 mg prednisone daily). * All subjects with brain metastases, except those meeting the following criteria: a. Brain metastases have been treated locally, and b. No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable) * Previous malignant disease (other than gastric cancer) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ (bladder,cervical, colorectal, breast) * Prior organ transplantation, including allogeneic stem-cell transplantation Significant acute or chronic infections * Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent * Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma) * Persisting toxicity of grade \>2 related to prior therapy except neuropathy and alopecia * Neuropathy Grade greater than or equal (\>=) 3. * Pregnancy or lactation * Known alcohol or drug abuse * History of uncontrolled intercurrent illness including hypertension, active infection, diabetes * Clinically significant (i.e., active) cardiovascular disease * All other significant diseases might impair the subject's tolerance of trial treatment * Any psychiatric condition that would prohibit the understanding or rendering of informed consent and that would limit compliance with study requirements * Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines * Legal incapacity or limited legal capacity * Subjects will be excluded from the treatment with irinotecan or paclitaxel monotherapy if administration of their chemotherapy would be inconsistent with the current local labeling (for example, in regard to contraindications, warnings/precautions, or special provisions) for that chemotherapy. Investigators should check updated labeling via relevant websites before randomization * Subjects should start treatment administration within 28 days after signing the informed consent form (ICF). Treatment administration will start within 4 days after the randomization call
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From randomization up to 627 days | OS was defined as the time from randomization to the date of death due to any cause. For participants who were still alive at the time of data analysis or who were lost to follow-up, OS time was censored at the date of last contact. OS was measured using Kaplan-Meier (KM) estimates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response (BOR) | From randomization up to 627 days | BOR was determined by RECIST v1.1 and defined as best-confirmed response of any of following: complete response (CR), partial response (PR), stable disease (SD) and PD recorded from date of randomization until disease progression or recurrence. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in SLD of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or appearance of 1 or more new lesions. PR or CR confirmed at a subsequent tumor assessment, not sooner than 5 weeks after initial documentation or at an assessment later than the next assessment after the initial documentation of PR or CR. SD confirmed at least 6 weeks after randomization. Confirmed PD equal to progression \<=2 weeks after date of randomization (and not qualifying for CR, PR or SD). |
| Objective Response Rate (ORR) | From randomization up to 627 days | The ORR defined as the percentage of all randomized participants with a confirmed best overall response (BOR) of partial response (PR),or complete response (CR) according to RECIST v1.1 and as adjudicated by the Independent Review Committee (IRC). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions. |
| Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT) | Baseline, EOT (up to Week 66) | EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall composite health state index score, with scores ranging from -0.594 to 1. A higher score indicates better health state. |
| Progression Free Survival (PFS) | From randomization up to 627 days | The PFS time was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause (whichever occurs first). PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier (KM) estimates. |
| Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status Scale Score at End of Treatment (EOT) | Baseline, EOT (up to Week 66) | EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnoea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact. The EORTC QLQ-C30 GHS/QoL score ranges from 0 to 100; High score indicates better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL. |
| Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Baseline, EOT (up to Week 66) | The EORTC QLQ-STO22 supplements the EORTC QLQ-C30 to assess symptoms and treatment-related side effects commonly reported in participants. There are 22 questions which comprise 5 scales (dysphagia, pain, reflux symptom, dietary restrictions, and anxiety) and 4 single items (dry mouth, hair loss, taste, body image). Most questions use 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms. |
| Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT) | Baseline, EOT (up to Week 66) | EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. |
Countries
Australia, Belgium, Czechia, France, Germany, Italy, Poland, South Korea, Spain, United States
Participant flow
Recruitment details
Overall, 459 participants were screened for this study. Of which, 371 participants were randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Physician Choice Chemotherapy + Best Supportive Care (BSC) Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m\^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m\^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion. | 186 |
| Avelumab + BSC Participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity along with BSC. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion. | 185 |
| Total | 371 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Participants randomized but not treated | 9 | 1 |
Baseline characteristics
| Characteristic | Avelumab + BSC | Total | Physician Choice Chemotherapy + Best Supportive Care (BSC) |
|---|---|---|---|
| Age, Continuous | 58.8 Years STANDARD_DEVIATION 11.66 | 59.5 Years STANDARD_DEVIATION 12.31 | 60.1 Years STANDARD_DEVIATION 12.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 30 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 153 Participants | 303 Participants | 150 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 17 Participants | 38 Participants | 21 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 47 Participants | 94 Participants | 47 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not collected/Missing | 15 Participants | 34 Participants | 19 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 119 Participants | 236 Participants | 117 Participants |
| Sex: Female, Male Female | 45 Participants | 104 Participants | 59 Participants |
| Sex: Female, Male Male | 140 Participants | 267 Participants | 127 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 131 / 177 | 142 / 184 |
| other Total, other adverse events | 150 / 177 | 146 / 184 |
| serious Total, serious adverse events | 81 / 177 | 90 / 184 |
Outcome results
Primary
Overall Survival (OS)
OS was defined as the time from randomization to the date of death due to any cause. For participants who were still alive at the time of data analysis or who were lost to follow-up, OS time was censored at the date of last contact. OS was measured using Kaplan-Meier (KM) estimates.
Time frame: From randomization up to 627 days
Population: FAS included all participants who were randomized to study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Overall Survival (OS) | 5.0 months |
| Avelumab + BSC | Overall Survival (OS) | 4.6 months |
p-value: 0.807895% CI: [0.88, 1.41]Log Rank
Secondary
Best Overall Response (BOR)
BOR was determined by RECIST v1.1 and defined as best-confirmed response of any of following: complete response (CR), partial response (PR), stable disease (SD) and PD recorded from date of randomization until disease progression or recurrence. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in SLD of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or appearance of 1 or more new lesions. PR or CR confirmed at a subsequent tumor assessment, not sooner than 5 weeks after initial documentation or at an assessment later than the next assessment after the initial documentation of PR or CR. SD confirmed at least 6 weeks after randomization. Confirmed PD equal to progression \<=2 weeks after date of randomization (and not qualifying for CR, PR or SD).
Time frame: From randomization up to 627 days
Population: FAS included all participants who were randomized to study treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Best Overall Response (BOR) | Non-complete response/ Non-progressive disease | 12 Participants |
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Best Overall Response (BOR) | Complete Response | 1 Participants |
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Best Overall Response (BOR) | Progressive disease | 59 Participants |
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Best Overall Response (BOR) | Stable disease | 62 Participants |
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Best Overall Response (BOR) | Non-evaluable | 45 Participants |
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Best Overall Response (BOR) | Partial response | 7 Participants |
| Avelumab + BSC | Best Overall Response (BOR) | Non-evaluable | 50 Participants |
| Avelumab + BSC | Best Overall Response (BOR) | Stable disease | 30 Participants |
| Avelumab + BSC | Best Overall Response (BOR) | Complete Response | 1 Participants |
| Avelumab + BSC | Best Overall Response (BOR) | Non-complete response/ Non-progressive disease | 7 Participants |
| Avelumab + BSC | Best Overall Response (BOR) | Progressive disease | 94 Participants |
| Avelumab + BSC | Best Overall Response (BOR) | Partial response | 3 Participants |
Secondary
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status Scale Score at End of Treatment (EOT)
EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnoea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact. The EORTC QLQ-C30 GHS/QoL score ranges from 0 to 100; High score indicates better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.
Time frame: Baseline, EOT (up to Week 66)
Population: HRQoL analysis set included a subset of the FAS and included FAS participants who met the following criteria: had 1 Baseline HRQoL assessment and had at least 1 post-Baseline HRQoL questionnaire completed. Number of Participants Analyzed signifies the number of participants analyzed in this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status Scale Score at End of Treatment (EOT) | -10.14 units on a scale | Standard Deviation 19.914 |
| Avelumab + BSC | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status Scale Score at End of Treatment (EOT) | -15.77 units on a scale | Standard Deviation 19.437 |
Secondary
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT)
The EORTC QLQ-STO22 supplements the EORTC QLQ-C30 to assess symptoms and treatment-related side effects commonly reported in participants. There are 22 questions which comprise 5 scales (dysphagia, pain, reflux symptom, dietary restrictions, and anxiety) and 4 single items (dry mouth, hair loss, taste, body image). Most questions use 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms.
Time frame: Baseline, EOT (up to Week 66)
Population: HRQoL analysis set included a subset of the FAS and included FAS participants who met the following criteria: had 1 Baseline HRQoL assessment and had at least 1 post-Baseline HRQoL questionnaire completed. Number of Participants Analyzed signifies the number of participants analyzed in this outcome.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Pain | 8.88 units on a scale | Standard Deviation 22.402 |
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Dry Mouth | 15.94 units on a scale | Standard Deviation 27.725 |
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Eating Restrictions | 9.24 units on a scale | Standard Deviation 22.661 |
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Tasting | 9.42 units on a scale | Standard Deviation 25.832 |
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Reflux | 4.59 units on a scale | Standard Deviation 20.184 |
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Body Image | 5.07 units on a scale | Standard Deviation 28.787 |
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Anxiety | 7.49 units on a scale | Standard Deviation 21.86 |
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Hair Loss | 4.71 units on a scale | Standard Deviation 33.546 |
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Dysphagia | 7.25 units on a scale | Standard Deviation 28.551 |
| Avelumab + BSC | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Hair Loss | -13.96 units on a scale | Standard Deviation 26.029 |
| Avelumab + BSC | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Dysphagia | 15.32 units on a scale | Standard Deviation 29.12 |
| Avelumab + BSC | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Pain | 9.23 units on a scale | Standard Deviation 21.527 |
| Avelumab + BSC | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Reflux | 7.96 units on a scale | Standard Deviation 18.347 |
| Avelumab + BSC | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Eating Restrictions | 13.29 units on a scale | Standard Deviation 21.276 |
| Avelumab + BSC | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Anxiety | 6.61 units on a scale | Standard Deviation 19.456 |
| Avelumab + BSC | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Dry Mouth | 9.01 units on a scale | Standard Deviation 28.827 |
| Avelumab + BSC | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Tasting | 2.25 units on a scale | Standard Deviation 35.897 |
| Avelumab + BSC | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) | Body Image | 4.05 units on a scale | Standard Deviation 27.561 |
Secondary
Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT)
EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall composite health state index score, with scores ranging from -0.594 to 1. A higher score indicates better health state.
Time frame: Baseline, EOT (up to Week 66)
Population: Health-related quality of life (HRQoL) analysis set included a subset of the FAS and included FAS participants who met the following criteria: had 1 Baseline HRQoL assessment, had at least 1 post-Baseline HRQoL questionnaire completed. Number of Participants Analyzed signifies the number of participants analyzed in this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT) | -0.103 units on a scale | Standard Deviation 0.2113 |
| Avelumab + BSC | Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT) | -0.144 units on a scale | Standard Deviation 0.2088 |
Secondary
Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT)
EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine.
Time frame: Baseline, EOT (up to Week 66)
Population: HRQoL analysis set included a subset of the FAS and included FAS participants who met the following criteria: had 1 Baseline HRQoL assessment, had at least 1 post-Baseline HRQoL questionnaire completed. Number of Participants Analyzed signifies the number of participants analyzed in this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT) | -12.3 millimeter (mm) | Standard Deviation 19.22 |
| Avelumab + BSC | Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT) | -13.6 millimeter (mm) | Standard Deviation 19.76 |
Secondary
Objective Response Rate (ORR)
The ORR defined as the percentage of all randomized participants with a confirmed best overall response (BOR) of partial response (PR),or complete response (CR) according to RECIST v1.1 and as adjudicated by the Independent Review Committee (IRC). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions.
Time frame: From randomization up to 627 days
Population: FAS included all participants who were randomized to study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Objective Response Rate (ORR) | 4.3 percentage of participants |
| Avelumab + BSC | Objective Response Rate (ORR) | 2.2 percentage of participants |
p-value: 0.8764Cochran-Mantel-Haenszel
Secondary
Progression Free Survival (PFS)
The PFS time was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause (whichever occurs first). PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier (KM) estimates.
Time frame: From randomization up to 627 days
Population: FAS included all participants who were randomized to study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Physician Choice Chemotherapy + Best Supportive Care (BSC) | Progression Free Survival (PFS) | 2.7 months |
| Avelumab + BSC | Progression Free Survival (PFS) | 1.4 months |
p-value: 195% CI: [1.36, 2.21]Log Rank