Triple Negative Breast Cancer
Conditions
Brief summary
This study will evaluate the efficacy, safety, and pharmacokinetics of adjuvant atezolizumab in combination with paclitaxel, followed by atezolizumab, dose-dense doxorubicin or epirubicin (investigator's choice), and cyclophosphamide, compared with paclitaxel followed by dose-dense doxorubicin or epirubicin (investigator's choice) and cyclophosphamide alone in patients with Stage II-III TNBC (Triple Negative Breast Cancer)
Interventions
DRUGAtezolizumab
Atezolizumab will be administered by IV, 840 mg every 2 weeks, for 10 doses. Atezolizumab maintenance will be administered by IV, 1200 mg every 3 weeks to complete 1 year
DRUGPaclitaxel
Paclitaxel will be administered by IV, 80 mg/m\^2 every week for 12 weeks.
DRUGDose-dense Doxorubicin or dose-dense Epirubicin
Dose-dense doxorubicin will be administered by IV, 60 mg/m\^2 every 2 weeks for a total of 4 doses. Or Dose-dense epirubicin will be administered by IV, (90 mg/m\^2) every 2 weeks for a total of 4 doses
DRUGCyclophosphamide
Cyclophosphamide will be administered by IV, 600 mg/m\^2 every 2 weeks for 4 doses
Sponsors
Breast International Group
Alliance Foundation Trials, LLC.
Jules Bordet Institute
Frontier Science & Technology Research Foundation, Inc.
Hoffmann-La Roche
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
* Non-metastatic operable Stage II-III breast cancer * Histologically documented TNBC (Triple Negative Breast Cancer) * Confirmed tumor PD-L1 evaluation as documented through central testing of a representative tumor tissue specimen * Adequately excised: Patients must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy * Adequate hematologic and end-organ function * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm. * No more than 8 weeks (56 days) may elapse between definitive breast surgery and randomization. * Representative formalin-fixed, paraffin embedded (FFPE) tumor specimen from surgical resection in paraffin blocks (preferred) or at least 25 unstained slides.
Exclusion criteria
* Prior history of invasive breast cancer * For the currently diagnosed breast cancer, any previous systemic anti-cancer treatment (e.g., neoadjuvant or adjuvant), including, but not limited to, chemotherapy, anti-HER2 therapy. * Previous therapy with anthracyclines or taxanes for any malignancy * Cardiopulmonary dysfunction * Prior malignancies within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome * Active or history of autoimmune disease or immune deficiency * History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan * Urinary outflow obstruction * Active tuberculosis * Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during study treatment or within 5 months following the last dose of Atezolizumab (for patients randomized to Atezolizumab) * Prior allogeneic stem cell or solid organ transplant * Treatment with systemic immunosuppressive medications within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressive medication during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Invasive Disease-Free Survival (iDFS) | From randomization until the occurrence of an iDFS event or death from any cause, whichever occurred earlier (up to 5 years) | iDFS was defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer involving the same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive breast cancer recurrence (an invasive breast cancer in the axilla, regional lymph nodes, chest wall, &/or skin of the ipsilateral breast); Ipsilateral second primary invasive breast cancer; Contralateral invasive breast cancer; Distant recurrence (evidence of breast cancer in any anatomic site \[other than the sites mentioned\]) that has either been histologically confirmed &/or clinically/radiographically diagnosed as recurrent invasive breast cancer; & Death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause. Analysis used Kaplan-Meier estimates where participants with no events at the time of analysis or no post-baseline information were censored. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Invasive Disease-Free Survival (iDFS) in the Node Positive Subpopulation | From randomization until the occurrence of an iDFS event or death from any cause, whichever occurred earlier (up to 5 years) | iDFS = the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer involving the same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive breast cancer recurrence (an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); Ipsilateral second primary invasive breast cancer; Contralateral invasive breast cancer; Distant recurrence (evidence of breast cancer in any anatomic site \[other than the sites mentioned\]) that has either been histologically confirmed and/or clinically/radiographically diagnosed as recurrent invasive breast cancer; and Death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause. Analysis used Kaplan-Meier estimates where participants with no events at the time of analysis or no post-baseline information were censored. |
| Overall Survival (OS) | From randomization up to death from any cause (up to 5 years) | Overall Survival (OS) is defined as the time from randomization to the date of death due to any cause. Analysis used Kaplan-Meier estimates where participants with no events at the time of analysis or no post-baseline information were censored. |
| Invasive Disease-Free Survival (iDFS) Including Second Primary Non-Breast Invasive Cancer | From randomization up to death from any cause (up to 5 years) | iDFS = the time from randomization until the date of first occurrence of one of the events: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer involving same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive breast cancer recurrence (an invasive breast cancer in axilla, regional lymph nodes, chest wall, &/or skin of the ipsilateral breast); Ipsilateral second primary invasive breast cancer; Second primary non-breast invasive cancer; Contralateral invasive breast cancer; Distant recurrence (i.e., evidence of breast cancer in any anatomic site \[other than sites mentioned\]) that has either been histologically confirmed &/or clinically/radiographically diagnosed as recurrent invasive breast cancer; Death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause. Analysis used Kaplan-Meier estimates where participants with no events at the time of analysis or no post-baseline information were censored. |
| Recurrence-Free Interval (RFI) | From randomization up to 5 years | Recurrence-Free Interval (RFI) was defined as the time from randomization to the first occurrence of any recurrence (local, regional \[including invasive ipsilateral tumor and invasive locoregional tumor\], or distant), as determined by investigators. Analysis used Kaplan-Meier estimates where participants with no events at the time of analysis, participants with no events who died, or participants with no post-baseline information were censored. |
| Distant Recurrence-Free Interval (DRFI) | From randomization up to 5 years | Distant Recurrence-Free Interval (DRFI) was defined as the time from randomization to the distant breast cancer recurrence. Analysis used Kaplan-Meier estimates where participants with no events at the time of analysis, participants with no events who died, or participants with no post-baseline information were censored. |
| Disease-Free Survival (DFS) | From randomization up to first disease recurrence or death from any cause (up to 5 years) | Disease-Free Survival (DFS) was defined as the time from randomization to the first occurrence of disease recurrence or death from any cause. DFS events include: Ipsilateral invasive breast tumor recurrence; Ipsilateral local-regional invasive breast cancer recurrence; Distant recurrence that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer; Contralateral invasive breast cancer; Ipsilateral or contralateral DCIS; Second primary non-breast invasive cancer; Death attributable to any cause. Analysis used Kaplan-Meier estimates where participants with no events at the time of analysis or no post-baseline information were censored. |
| Invasive Disease-Free Survival (iDFS) in the Subpopulation With Programmed Death-ligand 1 (PD-L1) Selected Tumor Status (IC1/2/3) | From randomization until the occurrence of an iDFS event or death from any cause, whichever occurred earlier (up to 5 years) | iDFS = the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer involving the same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive breast cancer recurrence (an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); Ipsilateral second primary invasive breast cancer, Contralateral invasive breast cancer, Distant recurrence (i.e., evidence of breast cancer in any anatomic site \[other than the sites mentioned\]) that has either been histologically confirmed and/or clinically/radiographically diagnosed as recurrent invasive breast cancer and Death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause. Analysis used Kaplan-Meier estimates where participants with no events at the time of analysis or no post-baseline information were censored. |
| Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | Baseline (Cycle 1 Day 1), Day 1 of Cycles 4, 6, 8, 10, 12, 14 & 16; end of treatment/discontinuation (approximately at Day 351); Follow up: Months 3 to 48 (Total duration is up to 5 years); Cycles 1-5= 28 day cycles; Cycles 6-16: 21 day cycles | The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. For the physical functioning scale, 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) were scored on a 4-point scale (1=Not at All to 4=Very Much). The scores were linearly transformed on a scale of 0 to 100, with a high score indicating worst functioning. Negative change from baseline indicated improvement in functioning. |
| Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | Baseline (Cycle 1 Day 1), Day 1 of Cycles 4, 6, 8, 10, 12, 14 & 16; end of treatment/discontinuation (approximately 351 days); Follow up: Months 3 to 48 (Total duration is up to 5 years); Cycles 1-5= 28 day cycles; Cycles 6-16: 21 day cycles | The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (Q29:GHS; How would you rate your overall health during the past week?) and Quality of Life (Q30: QoL; How would you rate your overall quality of life during the past week?) are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better outcome. Negative change from Baseline values indicated deterioration in QOL or functioning and positive values indicated improvement. |
| Number of Participants With Adverse Events (AE) | Up to 5 years | An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs are reported based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0. |
| Serum Concentration of Atezolizumab | Postdose Day 1 of Cycle 1; Predose Day 1 of Cycles 2, 3, and 4; Predose Cycles 6, 10, and 14; Predose Day 2 of Cycle 16; Cycles 1-5= 28-day cycles; Cycles 6-16: 21-day cycles | — |
| Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab | Up to 5 years | Baseline evaluable participant= participant with an ADA assay result from a baseline sample(s). Post-baseline evaluable participant= participant with an ADA assay result from at least one postbaseline sample. |
| Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | Baseline (Cycle 1 Day 1), Day 1 of Cycles 4, 6, 8, 10, 12, 14 & 16; end of treatment/discontinuation (approximately at Day 351); Follow up: Months 3 to 48 (Total duration is up to 5 years); Cycles 1-5= 28 day cycles; Cycles 6-16: 21 day cycles | The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. For the role functioning scale, participant responses to the 2 questions Q6: Were you limited in doing either your work or daily activities and Q7: Were you limited in pursuing your hobbies or other leisure time activities were scored on a 4-point scale (1=Not at All to 4=Very Much). The scores were linearly transformed on a scale of 0 to 100, with a low score indicating better functioning. Negative change from baseline indicated improvement. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, China, Czechia, Denmark, France, Germany, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Mexico, Peru, Poland, Romania, Russia, Singapore, South Korea, Spain, Switzerland, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Participants with newly diagnosed Stage II-III primary invasive Breast cancer (BC) that is of triple negative phenotype and who were to be treated with adjuvant systemic chemotherapy following definitive surgery, were enrolled in 342 centers in 31 countries.
Pre-assignment details
A total of 2199 participants were enrolled in the study. Participants were randomized in a 1:1 ratio to receive Atezolizumab and Chemotherapy or Chemotherapy alone.
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy Participants were administered paclitaxel, 80 mg/m\^2, IV infusion QW for maximum of 36 weeks followed by dose-dense doxorubicin, 60 mg/m\^2 or dose-dense epirubicin, 90 mg/m\^2 IV (investigator's choice) plus cyclophosphamide, 600 mg/m\^2, IV repeated every Q2W for a maximum of 20 weeks supported with G-CSF or GM-CSF treatment. | 1,098 |
| Atezolizumab and Chemotherapy Participants were administered atezolizumab 840 mg, IV infusion, Q2W in combination with chemotherapy (paclitaxel 80 mg/m\^2, IV infusion QW for maximum of 22 weeks followed by dose-dense doxorubicin, 60 mg/m\^2 or dose-dense epirubicin, 90 mg/m\^2, IV (investigator's choice) plus cyclophosphamide, 600 mg/m\^2, IV repeated Q2W for maximum of 17 weeks supported with G-CSF or GM-CSF treatment followed by atezolizumab, 1200 mg IV infusion every Q3W as a maintenance therapy to complete 1 year of atezolizumab treatment from the first dose. | 1,101 |
| Total | 2,199 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 58 | 72 |
| Overall Study | Disease Relapse | 0 | 1 |
| Overall Study | Lost to Follow-up | 15 | 26 |
| Overall Study | Physician Decision | 4 | 2 |
| Overall Study | Study Terminated By Sponsor | 933 | 927 |
| Overall Study | Withdrawal by Subject | 88 | 73 |
Baseline characteristics
| Characteristic | Atezolizumab and Chemotherapy | Total | Chemotherapy |
|---|---|---|---|
| Age, Continuous | 52.3 years STANDARD_DEVIATION 11.9 | 52.5 years STANDARD_DEVIATION 11.6 | 52.8 years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 75 Participants | 175 Participants | 100 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 950 Participants | 1856 Participants | 906 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 76 Participants | 168 Participants | 92 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 29 Participants | 57 Participants | 28 Participants |
| Race (NIH/OMB) Asian | 423 Participants | 824 Participants | 401 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 10 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 86 Participants | 185 Participants | 99 Participants |
| Race (NIH/OMB) White | 554 Participants | 1121 Participants | 567 Participants |
| Sex: Female, Male Female | 1101 Participants | 2195 Participants | 1094 Participants |
| Sex: Female, Male Male | 0 Participants | 4 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 58 / 1,098 | 72 / 1,101 |
| other Total, other adverse events | 1,068 / 1,084 | 1,082 / 1,093 |
| serious Total, serious adverse events | 173 / 1,084 | 280 / 1,093 |
Outcome results
Primary
Invasive Disease-Free Survival (iDFS)
iDFS was defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer involving the same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive breast cancer recurrence (an invasive breast cancer in the axilla, regional lymph nodes, chest wall, &/or skin of the ipsilateral breast); Ipsilateral second primary invasive breast cancer; Contralateral invasive breast cancer; Distant recurrence (evidence of breast cancer in any anatomic site \[other than the sites mentioned\]) that has either been histologically confirmed &/or clinically/radiographically diagnosed as recurrent invasive breast cancer; & Death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause. Analysis used Kaplan-Meier estimates where participants with no events at the time of analysis or no post-baseline information were censored.
Time frame: From randomization until the occurrence of an iDFS event or death from any cause, whichever occurred earlier (up to 5 years)
Population: ITT population included all randomized participants, whether or not the assigned study treatment was received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy | Invasive Disease-Free Survival (iDFS) | NA months |
| Atezolizumab and Chemotherapy | Invasive Disease-Free Survival (iDFS) | NA months |
p-value: 0.384695% CI: [0.87, 1.42]Log Rank
Secondary
Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7])
The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. For the role functioning scale, participant responses to the 2 questions Q6: Were you limited in doing either your work or daily activities and Q7: Were you limited in pursuing your hobbies or other leisure time activities were scored on a 4-point scale (1=Not at All to 4=Very Much). The scores were linearly transformed on a scale of 0 to 100, with a low score indicating better functioning. Negative change from baseline indicated improvement.
Time frame: Baseline (Cycle 1 Day 1), Day 1 of Cycles 4, 6, 8, 10, 12, 14 & 16; end of treatment/discontinuation (approximately at Day 351); Follow up: Months 3 to 48 (Total duration is up to 5 years); Cycles 1-5= 28 day cycles; Cycles 6-16: 21 day cycles
Population: Patient-reported outcome (PRO)-evaluable populations included participants in the ITT population with baseline PRO assessment and at least one post-baseline PRO assessment in the EORTC QLQC30. ITT population included all randomized participants, whether or not the assigned study treatment was received. Overall number 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 time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | Baseline | 87.26 score on scale | Standard Deviation 18.92 |
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Cycle 4 Day 1 | -10.88 score on scale | Standard Deviation 25 |
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Cycle 6 Day 1 | -17.31 score on scale | Standard Deviation 29.94 |
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Cycle 8 Day 1 | -4.58 score on scale | Standard Deviation 23.58 |
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Cycle 10 Day 1 | -3.77 score on scale | Standard Deviation 23.59 |
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Cycle 12 Day 1 | -1.53 score on scale | Standard Deviation 22.39 |
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Cycle 14 Day 1 | -1.02 score on scale | Standard Deviation 21.69 |
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Cycle 16 Day 1 | -1.09 score on scale | Standard Deviation 23.16 |
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Study Drug Completion/Early Discontinuation | -2.66 score on scale | Standard Deviation 23.48 |
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 3 | -0.26 score on scale | Standard Deviation 22.62 |
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 6 | 0.20 score on scale | Standard Deviation 24.08 |
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 9 | -0.18 score on scale | Standard Deviation 23.52 |
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 12 | 0.32 score on scale | Standard Deviation 22.42 |
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 18 | -0.47 score on scale | Standard Deviation 24.41 |
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 24 | 0.67 score on scale | Standard Deviation 23.54 |
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 30 | 2.24 score on scale | Standard Deviation 23.36 |
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 36 | 3.08 score on scale | Standard Deviation 23.57 |
| Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 48 | 0.00 score on scale | — |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 18 | 1.52 score on scale | Standard Deviation 21.82 |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | Baseline | 86.43 score on scale | Standard Deviation 19.66 |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 3 | -0.40 score on scale | Standard Deviation 23.34 |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Cycle 4 Day 1 | -10.26 score on scale | Standard Deviation 24.87 |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 48 | 13.33 score on scale | Standard Deviation 13.94 |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Cycle 6 Day 1 | -16.56 score on scale | Standard Deviation 29.18 |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 6 | 0.02 score on scale | Standard Deviation 24.03 |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Cycle 8 Day 1 | -4.58 score on scale | Standard Deviation 24.31 |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 24 | 1.74 score on scale | Standard Deviation 22.28 |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Cycle 10 Day 1 | -3.43 score on scale | Standard Deviation 22.77 |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 9 | 0.47 score on scale | Standard Deviation 23.35 |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Cycle 12 Day 1 | -1.59 score on scale | Standard Deviation 23.05 |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 36 | 4.74 score on scale | Standard Deviation 20.36 |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Cycle 14 Day 1 | -0.70 score on scale | Standard Deviation 20.61 |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 12 | 1.22 score on scale | Standard Deviation 21.95 |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Cycle 16 Day 1 | -0.10 score on scale | Standard Deviation 21.77 |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Follow-up Month 30 | 2.01 score on scale | Standard Deviation 24.19 |
| Atezolizumab and Chemotherapy | Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7]) | CFB: Study Drug Completion/Early Discontinuation | -4.37 score on scale | Standard Deviation 26.12 |
Secondary
Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score
The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (Q29:GHS; How would you rate your overall health during the past week?) and Quality of Life (Q30: QoL; How would you rate your overall quality of life during the past week?) are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better outcome. Negative change from Baseline values indicated deterioration in QOL or functioning and positive values indicated improvement.
Time frame: Baseline (Cycle 1 Day 1), Day 1 of Cycles 4, 6, 8, 10, 12, 14 & 16; end of treatment/discontinuation (approximately 351 days); Follow up: Months 3 to 48 (Total duration is up to 5 years); Cycles 1-5= 28 day cycles; Cycles 6-16: 21 day cycles
Population: PRO-evaluable populations included participants in the ITT population with baseline PRO assessment and at least one post-baseline PRO assessment in the EORTC QLQC30. ITT population included all randomized participants, whether or not the assigned study treatment was received. Overall number 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 time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | Baseline | 76.26 score on scale | Standard Deviation 18.15 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Cycle 4 Day 1 | -10.49 score on scale | Standard Deviation 20.25 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Cycle 6 Day 1 | -15.87 score on scale | Standard Deviation 23.83 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Cycle 8 Day 1 | -3.54 score on scale | Standard Deviation 19.72 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Cycle 10 Day 1 | -1.84 score on scale | Standard Deviation 19.57 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Cycle 12 Day 1 | -0.71 score on scale | Standard Deviation 19.41 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Cycle 14 Day 1 | -0.37 score on scale | Standard Deviation 19.04 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Cycle 16 Day 1 | 0.08 score on scale | Standard Deviation 18.56 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB:Study Drug Completion/Early Discontinuation | -1.56 score on scale | Standard Deviation 20.68 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 3 | 1.01 score on scale | Standard Deviation 20.25 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 6 | 1.10 score on scale | Standard Deviation 20.23 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 9 | 0.62 score on scale | Standard Deviation 20.47 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 12 | 1.21 score on scale | Standard Deviation 20.42 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 18 | 1.09 score on scale | Standard Deviation 22.18 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 24 | 2.32 score on scale | Standard Deviation 22.3 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 30 | 1.54 score on scale | Standard Deviation 21.36 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 36 | 2.64 score on scale | Standard Deviation 20.95 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 48 | 0.00 score on scale | — |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 18 | 0.47 score on scale | Standard Deviation 20.77 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | Baseline | 75.90 score on scale | Standard Deviation 18.52 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 3 | -0.74 score on scale | Standard Deviation 20.5 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Cycle 4 Day 1 | -10.02 score on scale | Standard Deviation 19.48 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 48 | 6.25 score on scale | Standard Deviation 31.46 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Cycle 6 Day 1 | -15.68 score on scale | Standard Deviation 22.32 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 6 | -0.90 score on scale | Standard Deviation 20.72 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Cycle 8 Day 1 | -5.09 score on scale | Standard Deviation 18.88 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 24 | 0.43 score on scale | Standard Deviation 21.33 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Cycle 10 Day 1 | -2.82 score on scale | Standard Deviation 18.38 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 9 | 0.07 score on scale | Standard Deviation 20.83 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Cycle 12 Day 1 | -2.31 score on scale | Standard Deviation 18.91 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 36 | 0.58 score on scale | Standard Deviation 23.57 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Cycle 14 Day 1 | -1.25 score on scale | Standard Deviation 18.35 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 12 | 0.19 score on scale | Standard Deviation 19.84 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Cycle 16 Day 1 | -1.30 score on scale | Standard Deviation 18.34 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB: Follow-up Month 30 | -0.57 score on scale | Standard Deviation 22.43 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score | CFB:Study Drug Completion/Early Discontinuation | -4.39 score on scale | Standard Deviation 22.01 |
Secondary
Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5])
The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. For the physical functioning scale, 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) were scored on a 4-point scale (1=Not at All to 4=Very Much). The scores were linearly transformed on a scale of 0 to 100, with a high score indicating worst functioning. Negative change from baseline indicated improvement in functioning.
Time frame: Baseline (Cycle 1 Day 1), Day 1 of Cycles 4, 6, 8, 10, 12, 14 & 16; end of treatment/discontinuation (approximately at Day 351); Follow up: Months 3 to 48 (Total duration is up to 5 years); Cycles 1-5= 28 day cycles; Cycles 6-16: 21 day cycles
Population: PRO-evaluable populations included participants in the ITT population with baseline PRO assessment and at least one post-baseline PRO assessment in the EORTC QLQC30. ITT population included all randomized participants, whether or not the assigned study treatment was received. Overall number 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 time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | Baseline | 89.86 score on scale | Standard Deviation 12.14 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Cycle 4 Day 1 | -8.93 score on scale | Standard Deviation 14.97 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Cycle 6 Day 1 | -13.30 score on scale | Standard Deviation 18.63 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Cycle 8 Day 1 | -5.33 score on scale | Standard Deviation 13.79 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Cycle 10 Day 1 | -3.71 score on scale | Standard Deviation 13.28 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Cycle 12 Day 1 | -2.41 score on scale | Standard Deviation 12.87 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Cycle 14 Day 1 | -1.41 score on scale | Standard Deviation 12.87 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Cycle 16 Day 1 | -1.65 score on scale | Standard Deviation 12.78 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB:Study Drug Completion/Early Discontinuation | -2.56 score on scale | Standard Deviation 13.72 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB:Follow-up Month 3 | -1.62 score on scale | Standard Deviation 12.71 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Follow-up Month 6 | -1.70 score on scale | Standard Deviation 13.46 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Follow-up Month 9 | -1.55 score on scale | Standard Deviation 13.75 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Follow-up Month 12 | -1.70 score on scale | Standard Deviation 13.85 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Follow-up Month 18 | -1.92 score on scale | Standard Deviation 13.6 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Follow-up Month 24 | -1.37 score on scale | Standard Deviation 13.89 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Follow-up Month 30 | -1.61 score on scale | Standard Deviation 15.61 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Follow-up Month 36 | -0.42 score on scale | Standard Deviation 14.4 |
| Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Follow-up Month 48 | -13.33 score on scale | — |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Follow-up Month 18 | -0.91 score on scale | Standard Deviation 13.79 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | Baseline | 89.92 score on scale | Standard Deviation 11.57 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB:Follow-up Month 3 | -2.29 score on scale | Standard Deviation 13.47 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Cycle 4 Day 1 | -8.69 score on scale | Standard Deviation 14.91 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Follow-up Month 48 | -2.67 score on scale | Standard Deviation 3.65 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Cycle 6 Day 1 | -13.55 score on scale | Standard Deviation 18.47 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Follow-up Month 6 | -1.96 score on scale | Standard Deviation 13.78 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Cycle 8 Day 1 | -6.42 score on scale | Standard Deviation 14.41 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Follow-up Month 24 | -0.72 score on scale | Standard Deviation 12.91 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Cycle 10 Day 1 | -4.42 score on scale | Standard Deviation 13.15 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Follow-up Month 9 | -1.33 score on scale | Standard Deviation 13.91 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Cycle 12 Day 1 | -3.42 score on scale | Standard Deviation 12.95 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Follow-up Month 36 | 0.82 score on scale | Standard Deviation 13.18 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Cycle 14 Day 1 | -1.92 score on scale | Standard Deviation 12.11 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Follow-up Month 12 | -1.37 score on scale | Standard Deviation 13.39 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Cycle 16 Day 1 | -1.82 score on scale | Standard Deviation 12.12 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB: Follow-up Month 30 | -0.74 score on scale | Standard Deviation 12.72 |
| Atezolizumab and Chemotherapy | Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5]) | CFB:Study Drug Completion/Early Discontinuation | -4.68 score on scale | Standard Deviation 16.69 |
Secondary
Disease-Free Survival (DFS)
Disease-Free Survival (DFS) was defined as the time from randomization to the first occurrence of disease recurrence or death from any cause. DFS events include: Ipsilateral invasive breast tumor recurrence; Ipsilateral local-regional invasive breast cancer recurrence; Distant recurrence that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer; Contralateral invasive breast cancer; Ipsilateral or contralateral DCIS; Second primary non-breast invasive cancer; Death attributable to any cause. Analysis used Kaplan-Meier estimates where participants with no events at the time of analysis or no post-baseline information were censored.
Time frame: From randomization up to first disease recurrence or death from any cause (up to 5 years)
Population: ITT population included all randomized participants, whether or not the assigned study treatment was received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy | Disease-Free Survival (DFS) | NA months |
| Atezolizumab and Chemotherapy | Disease-Free Survival (DFS) | NA months |
Secondary
Distant Recurrence-Free Interval (DRFI)
Distant Recurrence-Free Interval (DRFI) was defined as the time from randomization to the distant breast cancer recurrence. Analysis used Kaplan-Meier estimates where participants with no events at the time of analysis, participants with no events who died, or participants with no post-baseline information were censored.
Time frame: From randomization up to 5 years
Population: ITT population included all randomized participants, whether or not the assigned study treatment was received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy | Distant Recurrence-Free Interval (DRFI) | NA months |
| Atezolizumab and Chemotherapy | Distant Recurrence-Free Interval (DRFI) | NA months |
Secondary
Invasive Disease-Free Survival (iDFS) Including Second Primary Non-Breast Invasive Cancer
iDFS = the time from randomization until the date of first occurrence of one of the events: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer involving same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive breast cancer recurrence (an invasive breast cancer in axilla, regional lymph nodes, chest wall, &/or skin of the ipsilateral breast); Ipsilateral second primary invasive breast cancer; Second primary non-breast invasive cancer; Contralateral invasive breast cancer; Distant recurrence (i.e., evidence of breast cancer in any anatomic site \[other than sites mentioned\]) that has either been histologically confirmed &/or clinically/radiographically diagnosed as recurrent invasive breast cancer; Death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause. Analysis used Kaplan-Meier estimates where participants with no events at the time of analysis or no post-baseline information were censored.
Time frame: From randomization up to death from any cause (up to 5 years)
Population: ITT population included all randomized participants, whether or not the assigned study treatment was received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy | Invasive Disease-Free Survival (iDFS) Including Second Primary Non-Breast Invasive Cancer | NA months |
| Atezolizumab and Chemotherapy | Invasive Disease-Free Survival (iDFS) Including Second Primary Non-Breast Invasive Cancer | NA months |
Secondary
Invasive Disease-Free Survival (iDFS) in the Node Positive Subpopulation
iDFS = the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer involving the same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive breast cancer recurrence (an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); Ipsilateral second primary invasive breast cancer; Contralateral invasive breast cancer; Distant recurrence (evidence of breast cancer in any anatomic site \[other than the sites mentioned\]) that has either been histologically confirmed and/or clinically/radiographically diagnosed as recurrent invasive breast cancer; and Death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause. Analysis used Kaplan-Meier estimates where participants with no events at the time of analysis or no post-baseline information were censored.
Time frame: From randomization until the occurrence of an iDFS event or death from any cause, whichever occurred earlier (up to 5 years)
Population: Node positive subpopulation included all participants in the ITT population whose lymph node (LN) status was positive at the time of randomization. ITT population included all randomized participants, whether or not the assigned study treatment was received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy | Invasive Disease-Free Survival (iDFS) in the Node Positive Subpopulation | NA months |
| Atezolizumab and Chemotherapy | Invasive Disease-Free Survival (iDFS) in the Node Positive Subpopulation | NA months |
Secondary
Invasive Disease-Free Survival (iDFS) in the Subpopulation With Programmed Death-ligand 1 (PD-L1) Selected Tumor Status (IC1/2/3)
iDFS = the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer involving the same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive breast cancer recurrence (an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); Ipsilateral second primary invasive breast cancer, Contralateral invasive breast cancer, Distant recurrence (i.e., evidence of breast cancer in any anatomic site \[other than the sites mentioned\]) that has either been histologically confirmed and/or clinically/radiographically diagnosed as recurrent invasive breast cancer and Death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause. Analysis used Kaplan-Meier estimates where participants with no events at the time of analysis or no post-baseline information were censored.
Time frame: From randomization until the occurrence of an iDFS event or death from any cause, whichever occurred earlier (up to 5 years)
Population: PD-L1-positive subpopulation included participants in the ITT population whose PD-L1 status was IC1/2/3 at the time of randomization. ITT population included all randomized participants, whether or not the assigned study treatment was received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy | Invasive Disease-Free Survival (iDFS) in the Subpopulation With Programmed Death-ligand 1 (PD-L1) Selected Tumor Status (IC1/2/3) | NA months |
| Atezolizumab and Chemotherapy | Invasive Disease-Free Survival (iDFS) in the Subpopulation With Programmed Death-ligand 1 (PD-L1) Selected Tumor Status (IC1/2/3) | NA months |
Secondary
Number of Participants With Adverse Events (AE)
An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs are reported based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.
Time frame: Up to 5 years
Population: Safety Evaluable Population included all participants who received any amount of any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy | Number of Participants With Adverse Events (AE) | 1074 Participants |
| Atezolizumab and Chemotherapy | Number of Participants With Adverse Events (AE) | 1090 Participants |
Secondary
Overall Survival (OS)
Overall Survival (OS) is defined as the time from randomization to the date of death due to any cause. Analysis used Kaplan-Meier estimates where participants with no events at the time of analysis or no post-baseline information were censored.
Time frame: From randomization up to death from any cause (up to 5 years)
Population: ITT population included all randomized participants, whether or not the assigned study treatment was received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy | Overall Survival (OS) | NA months |
| Atezolizumab and Chemotherapy | Overall Survival (OS) | NA months |
Secondary
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
Baseline evaluable participant= participant with an ADA assay result from a baseline sample(s). Post-baseline evaluable participant= participant with an ADA assay result from at least one postbaseline sample.
Time frame: Up to 5 years
Population: Safety Evaluable Population included all participants who received any amount of any study drug. Number analyzed at baseline and postbaseline are unique number of participants out of all the assessed participants who may have been ADA positive at that timepoint. Different participants may have contributed data for baseline and postbaseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chemotherapy | Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab | Baseline | 2.1 percentage of participants |
| Chemotherapy | Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab | Post-baseline | 11.5 percentage of participants |
Secondary
Recurrence-Free Interval (RFI)
Recurrence-Free Interval (RFI) was defined as the time from randomization to the first occurrence of any recurrence (local, regional \[including invasive ipsilateral tumor and invasive locoregional tumor\], or distant), as determined by investigators. Analysis used Kaplan-Meier estimates where participants with no events at the time of analysis, participants with no events who died, or participants with no post-baseline information were censored.
Time frame: From randomization up to 5 years
Population: ITT population included all randomized participants, whether or not the assigned study treatment was received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy | Recurrence-Free Interval (RFI) | NA months |
| Atezolizumab and Chemotherapy | Recurrence-Free Interval (RFI) | NA months |
Secondary
Serum Concentration of Atezolizumab
Time frame: Postdose Day 1 of Cycle 1; Predose Day 1 of Cycles 2, 3, and 4; Predose Cycles 6, 10, and 14; Predose Day 2 of Cycle 16; Cycles 1-5= 28-day cycles; Cycles 6-16: 21-day cycles
Population: Pharmacokinetic (PK)-evaluable population included all participants who received any dose of study medication and who have at least one evaluable postbaseline PK sample. Overall number 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 time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Chemotherapy | Serum Concentration of Atezolizumab | Pre-dose: Cycle 4 Day 1 | 221 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 120.4 |
| Chemotherapy | Serum Concentration of Atezolizumab | Post-dose: Cycle 1 Day 1 | 319 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 43.3 |
| Chemotherapy | Serum Concentration of Atezolizumab | Pre-dose: Cycle 2 Day 1 | 153 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 85.2 |
| Chemotherapy | Serum Concentration of Atezolizumab | Pre-dose: Cycle 3 Day 1 | 220 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 62 |
| Chemotherapy | Serum Concentration of Atezolizumab | Pre-dose: Cycle 6 | 239 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 146.9 |
| Chemotherapy | Serum Concentration of Atezolizumab | Pre-dose: Cycle 10 | 250 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 92.2 |
| Chemotherapy | Serum Concentration of Atezolizumab | Pre-dose: Cycle 14 | 258 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 118.7 |
| Chemotherapy | Serum Concentration of Atezolizumab | Pre-dose: Cycle 16 Day 2 | 355 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 29.5 |