Non-Small Cell Lung Cancer
Conditions
Brief summary
This multicenter, open-label, randomized study will evaluate the efficacy and safety of Atezolizumab compared with docetaxel in participants with advanced or metastatic non-small cell lung cancer after platinum failure. Participants will be randomized to receive either Atezolizumab 1200 milligram (mg) intravenously every 3 weeks or docetaxel 75 milligram per meter square (mg/m\^2) intravenously every 3 weeks. Treatment with Atezolizumab may be continued as long as participants are experiencing clinical benefit as assessed by the investigator, i.e., in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression.
Interventions
DRUGDocetaxel
Participants received starting dose of 75 mg/m\^2 every three week (q3w) until disease progression, unacceptable toxicity or death. Dose modifications were according to the locally approved label. Participants randomized to receive docetaxel had to be premedicated with corticosteroids according to local practice.
DRUGAtezolizumab
Participants received atezolizumab of 1200 mg (equivalent to an average body weight-based dose of 15 milligram per kilogram \[mg/kg\]) which was administered by IV infusion q3w on Day 1 of each 21 day cycle. Participants were allowed to continue treatment beyond progression per response evaluation criteria in solid tumors (RECIST) v1.1 if they were experiencing clinical benefit per investigator, did not have a decline in performance status, did not have signs or symptoms of unequivocal progression, did not have tumor progression at critical sites, and signed an informed consent signature page acknowledging deferment any standard treatment options that may exist in favor of continuing atezolizumab.
Sponsors
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
* Adult participants, \>/= 18 years of age * Locally advanced or metastatic (Stage IIIB, Stage IV, or recurrent) non-small cell lung cancer (NSCLC) * Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens * Disease progression during or following treatment with a prior platinum-containing regimen for locally advanced, unresectable/inoperable or metastatic NSCLC or disease recurrence within 6 months of treatment with a platinum-based adjuvant/neoadjuvant regimen * Measurable disease, as defined by RECIST v1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion criteria
* Known active or untreated central nervous system (CNS) metastases as determined by CT or MRI evaluation during screening and prior radiographic assessments * Malignancies other than NSCLC 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 * History of autoimmune disease * History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted. * Active hepatitis B or hepatitis C * Prior treatment with docetaxel * Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From the time of randomization to the date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months) | Overall Survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as dead at the time of analysis was censored at the date when they were last known to be alive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Baseline until date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months) | ORR was defined as the percentage of participants with confirmed objective tumor response, complete response (CR) or partial response (PR), as determined by investigator using RECIST v1.1 criteria. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. |
| Progression-Free Survival (PFS) | From the time of randomization to the date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months) | PFS was defined as the time (in months) between the date of randomization and the date of first documented disease progression or death, whichever occurs first. Disease progression was determined based on investigator assessment using response evaluation criteria In solid tumors (RECIST) v1.1. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions including baseline In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. |
| Duration of Response (DOR) | From the time of randomization to the date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months) | DOR was defined as the duration from the first tumor assessment that supports the participant's objective response (CR or PR, whichever is first recorded) to disease progression or death due to any cause, whichever occurs first. |
| ORR (Modified RECIST) | From the time of randomization to the date of death due to any cause or up to data cut off date: 08 May 2015 (up to 21 months) | ORR was defined as the percentage of participants with confirmed objective tumor response, CR or PR, as determined by investigator using modified RECIST criteria. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to l\< 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. |
| PFS (Modified RECIST) | From the time of randomization to the date of death due to any cause or up to data cut off date: 08 May 2015 (up to 21 months) | PFS was defined as the time (in months) between the date of randomization and the date of first documented disease progression or death, whichever occurs first. Disease progression was determined based on investigator assessment using modified RECIST criteria. PD: at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. |
| DOR (Modified RECIST) | From the time of randomization to the date of death due to any cause or up to data cut off date: 08 May 2015 (up to 21 months) | DOR was defined as the duration from the first tumor assessment that supports the participant's objective response (CR or PR, whichever is first recorded) to disease progression or death due to any cause, whichever occurs first. |
Countries
Belgium, Canada, France, Germany, Italy, Poland, South Korea, Spain, Sweden, Thailand, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
A total of 527 participants were screened, of whom 287 participants were randomized. 143 participants to the docetaxel arm and 144 participants to the atezolizumab arm. Overall, 10 participants (8 in the docetaxel arm and 2 in the atezolizumab arm) did not receive any study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel Participants received docetaxel 75 milligram per squared meters (mg/m\^2) administered intravenously on Day 1 of each 21 day cycle until disease progression or unacceptable toxicity or death. | 143 |
| Atezolizumab Participants were administered atezolizumab intravenously on Day 1 of each 21 day cycle at a fixed dose of 1200 mg. Atezolizumab treatment were to continued as long as participants were experiencing clinical benefit as assessed by the investigator. | 144 |
| Total | 287 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 118 | 121 |
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Study Terminated by Sponsor | 8 | 14 |
| Overall Study | Terminated by Sponsor After 31 Aug 2018 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 15 | 4 |
Baseline characteristics
| Characteristic | Docetaxel | Atezolizumab | Total |
|---|---|---|---|
| Age, Continuous | 61.8 years STANDARD_DEVIATION 9.4 | 61.5 years STANDARD_DEVIATION 9.2 | 61.6 years STANDARD_DEVIATION 9.3 |
| Sex: Female, Male Female | 67 Participants | 51 Participants | 118 Participants |
| Sex: Female, Male Male | 76 Participants | 93 Participants | 169 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 118 / 143 | 121 / 144 |
| other Total, other adverse events | 125 / 135 | 127 / 142 |
| serious Total, serious adverse events | 46 / 135 | 53 / 142 |
Outcome results
Primary
Overall Survival (OS)
Overall Survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as dead at the time of analysis was censored at the date when they were last known to be alive.
Time frame: From the time of randomization to the date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months)
Population: ITT population for efficacy analyses included all randomized participants, regardless of whether they received any study drug. In the efficacy analyses, the ITT population, participants were grouped according to the treatment arm to which they were assigned.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel | Overall Survival (OS) | 9.7 months |
| Atezolizumab | Overall Survival (OS) | 12.6 months |
Comparison: Hazard ratios (HR) were estimated by a Cox regression model.p-value: =0.010695% CI: [0.52, 0.92]Log rank (Stratified)
Secondary
DOR (Modified RECIST)
DOR was defined as the duration from the first tumor assessment that supports the participant's objective response (CR or PR, whichever is first recorded) to disease progression or death due to any cause, whichever occurs first.
Time frame: From the time of randomization to the date of death due to any cause or up to data cut off date: 08 May 2015 (up to 21 months)
Population: ITT population for efficacy analyses included all randomized participants, regardless of whether they received any study drug. Here, number of participants analyzed signifies the number of participants who were evaluable for this outcome measure. The data was planned to be reported for Atezolizumab arm only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel | DOR (Modified RECIST) | 14.9 months |
Secondary
Duration of Response (DOR)
DOR was defined as the duration from the first tumor assessment that supports the participant's objective response (CR or PR, whichever is first recorded) to disease progression or death due to any cause, whichever occurs first.
Time frame: From the time of randomization to the date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months)
Population: ITT population for efficacy analyses included all randomized participants, regardless of whether they received any study drug. Here, number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel | Duration of Response (DOR) | 7.2 months |
| Atezolizumab | Duration of Response (DOR) | 18.6 months |
Comparison: HR were estimated by a unstratified Cox regression model.p-value: =0.002895% CI: [0.15, 0.7]Log rank (unstratified)
Secondary
Objective Response Rate (ORR)
ORR was defined as the percentage of participants with confirmed objective tumor response, complete response (CR) or partial response (PR), as determined by investigator using RECIST v1.1 criteria. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time frame: Baseline until date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months)
Population: ITT population for efficacy analyses included all randomized participants, regardless of whether they received any study drug. In the efficacy analyses, the ITT population, participants were grouped according to the treatment arm to which they were assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel | Objective Response Rate (ORR) | 14.7 percentage of participants |
| Atezolizumab | Objective Response Rate (ORR) | 15.3 percentage of participants |
p-value: =0.888495% CI: [-7.67, 8.85]Cochran-Mantel-Haenszel
Secondary
ORR (Modified RECIST)
ORR was defined as the percentage of participants with confirmed objective tumor response, CR or PR, as determined by investigator using modified RECIST criteria. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to l\< 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time frame: From the time of randomization to the date of death due to any cause or up to data cut off date: 08 May 2015 (up to 21 months)
Population: ITT population for efficacy analyses included all randomized participants, regardless of whether they received any study drug. In the efficacy analyses, the ITT population, participants were grouped according to the treatment arm to which they were assigned. The data was planned to be reported for Atezolizumab arm only
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel | ORR (Modified RECIST) | 16.7 percentage of participants |
Secondary
PFS (Modified RECIST)
PFS was defined as the time (in months) between the date of randomization and the date of first documented disease progression or death, whichever occurs first. Disease progression was determined based on investigator assessment using modified RECIST criteria. PD: at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Time frame: From the time of randomization to the date of death due to any cause or up to data cut off date: 08 May 2015 (up to 21 months)
Population: ITT population for efficacy analyses included all randomized participants, regardless of whether they received any study drug. In the efficacy analyses, the ITT population, participants were grouped according to the treatment arm to which they were assigned. The data was planned to be reported for Atezolizumab arm only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel | PFS (Modified RECIST) | 4.2 months |
Secondary
Progression-Free Survival (PFS)
PFS was defined as the time (in months) between the date of randomization and the date of first documented disease progression or death, whichever occurs first. Disease progression was determined based on investigator assessment using response evaluation criteria In solid tumors (RECIST) v1.1. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions including baseline In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Time frame: From the time of randomization to the date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months)
Population: ITT population for efficacy analyses included all randomized participants, regardless of whether they received any study drug. In the efficacy analyses, the ITT population, participants were grouped according to the treatment arm to which they were assigned.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel | Progression-Free Survival (PFS) | 3.4 months |
| Atezolizumab | Progression-Free Survival (PFS) | 2.7 months |
Comparison: HR were estimated by a Cox regression model. The two treatment comparison was based on a stratified log-rank test.p-value: =0.556395% CI: [0.71, 1.2]Log rank (Stratified)