IMpower150: Increased OS With Atezolizumab/Bevacizumab Plus Chemotherapy in Advanced Nonsquamous NSCLC
The phase III IMpower150 study met its coprimary endpoint of overall survival (OS) at interim analysis and showed that first-line treatment with the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) plus carboplatin and paclitaxel (chemotherapy) helped patients with advanced nonsquamous non–small cell lung cancer (NSCLC) live significantly longer compared with bevacizumab plus carboplatin and paclitaxel. A survival benefit was observed across key subgroups, including those with varying levels of programmed cell death ligand 1 (PD-L1) expression. Safety for the atezolizumab and bevacizumab plus carboplatin and paclitaxel combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combinations. These data will be presented at an upcoming oncology congress.
At this interim analysis, the study found that substituting bevacizumab with atezolizumab in the combination with carboplatin and paclitaxel did not show a statistically significant OS benefit in people with advanced NSCLC compared to a combination of bevacizumab plus carboplatin and paclitaxel. The study will continue as planned to the final analysis. Safety in the atezolizumab plus carboplatin and paclitaxel arm appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination.
Previously reported results from the IMpower150 study showed that the combination of atezolizumab and bevacizumab plus carboplatin and paclitaxel reduced the risk of progression-free survival (PFS), a coprimary endpoint, by 38% (hazard ratio [HR] = 0.62; P < .0001, 95% confidence interval [CI] = 0.52–0.74) compared to bevacizumab plus carboplatin and paclitaxel in the first-line treatment of people with advanced nonsquamous NSCLC. This PFS benefit was observed across key subgroups, including those with varying levels of PD-L1 expression.
More About IMpower150
IMpower150 is a multicenter, open-label, randomized, controlled phase III study evaluating the efficacy and safety of atezolizumab in combination with carboplatin and paclitaxel with or without bevacizumab in people with stage IV nonsquamous NSCLC who had not been treated with chemotherapy for their advanced disease. It enrolled 1,202 patients, of which those with ALK and EGFR mutations were excluded from the primary intention-to-treat (ITT) analysis. Patients were randomized (1:1:1) to receive:
- Atezolizumab plus carboplatin and paclitaxel (Arm A)
- Atezolizumab and bevacizumab plus carboplatin and paclitaxel (Arm B)
- Bevacizumab plus carboplatin and paclitaxel (Arm C, control arm)
During the treatment-induction phase, patients in Arm A received atezolizumab administered intravenously at 1,200 mg in combination with intravenous infusion of carboplatin and paclitaxel on day 1 of a 3-week treatment cycle for 4 or 6 cycles. Following the induction phase, people received maintenance treatment with atezolizumab (1,200 mg every 3 weeks) until loss of clinical benefit or disease progression.
Patients in Arm B received induction treatment with atezolizumab (1,200 mg) and bevacizumab administered intravenously at 15 mg/kg in combination with intravenous infusion of carboplatin and paclitaxel on day 1 of a 3-week treatment cycle for 4 or 6 cycles. People then received maintenance treatment with the atezolizumab and bevacizumab regimen until disease progression (bevacizumab) or loss of clinical benefit/disease progression (atezolizumab).
Patients in Arm C received induction treatment with bevacizumab administered intravenously at 15 mg/kg plus intravenous infusion of carboplatin and paclitaxel on day 1 of a 3-week treatment cycle for 4 or 6 cycles. This was followed by maintenance treatment with bevacizumab alone until disease progression.?
The coprimary endpoints were PFS and OS, as determined by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). The coprimary OS endpoint in IMpower150 was assessed in all randomized people without an ALK or EGFR genetic mutation (intention-to-treat wild-type). Key secondary endpoints included investigator-assessed PFS and OS, and safety in the ITT population and in EGFR and ALK mutation subgroups. The primary analysis of the coprimary PFS endpoint in IMpower150 was assessed in two populations: all randomized patients without an ALK or EGFR genetic mutation (intention-to-treat wild-type) and in a subgroup of patients who had a specific biomarker (T-effector “Teff” gene signature expression).
IMpower150 met its PFS coprimary endpoint per study protocol for both populations assessed.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
