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Bunn Expands on Significance of Atezolizumab/Bevacizumab Regimen in NSCLC

Danielle Bucco
Published: Tuesday, Jan 16, 2018

Paul A. Bunn Jr, MD
Paul A. Bunn Jr, MD
Findings from the phase III IMpower150 trial presented at the 2017 ESMO Immuno-Oncology Congress demonstrated that treatment with the combination of atezolizumab (Tecentriq), bevacizumab (Avastin), carboplatin, and paclitaxel delayed progression or death by 38% compared with bevacizumab and chemotherapy alone for patients with nonsquamous non–small cell lung cancer (NSCLC).

The IMpower150 study enrolled 1202 patients with stage IV nonsquamous NSCLC. Patients were randomized to receive atezolizumab plus carboplatin and paclitaxel (arm A), atezolizumab with bevacizumab plus carboplatin and paclitaxel (arm B), or bevacizumab plus carboplatin and paclitaxel (arm C). Progression-free survival (PFS) and overall survival (OS) were the primary endpoints.

The atezolizumab combination elicited a median PFS of 8.3 months compared with 6.8 months with bevacizumab and chemotherapy alone (HR, 0.62; 95% CI, 0.52-0.74; P <.0001). After a minimum follow-up of 9.5 months, the median OS was 14.4 months (95% CI, 12.8-17.1) versus 19.2 months (95% CI, 16.8-26.1), in favor of the atezolizumab group (HR, 0.775; 95% CI, 0.619-0.970; P = .0262).

In an interview with OncLive, Paul A. Bunn, Jr, MD, distinguished professor, Division of Medical Oncology/University of Colorado, James Dudley Chair in Lung Cancer Research, University of Colorado Denver, 2014 Giant of Cancer Care® in Lung Cancer, shared his expert opinion on the IMpower150 study and other immunotherapy combinations in NSCLC.

OncLive: Can you discuss the results of the IMpower150 study?

Bunn: One issue about immunotherapy is that a minority of patients respond to it—that is, only about 20%. Therefore, we were wondering if you combined a single-agent checkpoint inhibitor with other immunotherapies, chemotherapies, or antiangiogenic agents, would you have a higher response rate and better overall outcome?

This trial was designed to determine whether the addition of atezolizumab to chemotherapy would be better than chemotherapy alone. This is a phase III randomized trial that reported on this combination. However, cohort G of the KEYNOTE-021 trial was a randomized phase II trial that already reported on a similar combination. Additionally, there are a number of other trials that have released preliminary information, including KEYNOTE-189, MYSTIC, and CheckMate-227. 

This is the first trial that looked at chemotherapy versus chemotherapy plus a checkpoint inhibitor to present randomized phase III data. It is always better to be first; however, the combination of pembrolizumab (Keytruda) with chemotherapy for nonsquamous NSCLC has already been approved by the FDA because of randomized phase II data. 

How does the pembrolizumab and chemotherapy combination compare with the atezolizumab combination?

The median OS in cohort G of KEYNOTE-021 had not been reached for the combination arm. However, at 18 months, 70% of patients were alive and the OS for the chemotherapy arm was 20.9 months. The IMpower150 trial is a similar population, but the median OS for arm B was 19.2 months. In this study, at 18 months, 55% of patients were alive. The chemotherapy arm had an OS of 14.4 months. They are different trials, making it difficult to compare, but the long-term survival of the atezolizumab combination does not seem quite as good as the pembrolizumab combination.

The chemotherapy arm, arm A, in the IMpower150 study is not as good as the bevacizumab arm. Cross comparisons are complicated, but 4-drug combinations are going to be more expensive than 3-drug combinations. In general, OS tends to become more impressive as time goes on. These data were from an early time.


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