POPLAR: Inhibition of the PD-L1/PD-1 pathway may improve survival in NSCLC

Issue: July 25, 2015

CHICAGO — Patients with non–small cell lung cancer with high PD-L1 expression benefitted from treatment with the novel anti-PD-L1 agent atezolizumab, according to findings presented at the ASCO Annual Meeting.

Perspective from Wallace Akerley, MD; Marina Chiara Garassino, MD

Alexander I. Spira, MD, PhD, FACP, director of the Virginia Cancer Specialists Research Institute in Fairfax, Virginia, and colleagues evaluated atezolizumab (Genentech/Roche) —formerly known as MPDL3280A — in a cohort of 287 previously treated patients with NSCLC.

Researchers stratified patients by PD-L1 immune cell status, histology and previous lines of therapy. Treatment regimens included 1,200 mg of the study drug administered intravenously every 3 weeks or 75 mg/m² IV docetaxel every 3 weeks.

Researchers evaluated patients’ PD-L1 expression using immunohistochemistry and defined expression as scores ranging from 0 to 3 for tumor cell and immune cell expression.

OS served as the primary endpoint.

Median OS in the intent-to-treat analysis was 11.4 months in the atezolizumab group and 9.5 months in the docetaxel group (HR = 0.78; 95% CI, 0.59-1.03).

Efficacy results indicated that the study drug was most effective in patients with higher PD-L1 expression. OS among patients with the highest levels (score 3) of PD-L1–positive tumor cells and immune cells was not reached vs. 11.1 months for docetaxel (HR = 0.47; 95% CI, 0.20-1.11). Further, among patients with any level of PD-L1 expression other than 0, the median OS was not reached in the atezolizumab arm and 9.1 months in the docetaxel arm (HR = 0.63; 95% CI, 0.42-0.95).

By comparison, median OS was 9.7 months in both study arms among patients with tumor cell 0 and immune cell 0 scores (HR = 1.22; 95% CI, 0.69-2.14).

Overall, median PFS rates were 2.8 months for atezolizumab and 3.4 months for docetaxel (HR = 0.96; 95% CI, 0.76-1.2) in the intent-to-treat analysis.

Median PFS in the highest PD-L1 expression group also improved with atezolizumab (9.7 months vs. 3.9 months; HR = 0.57; 95% CI, 0.28-1.11). Conversely, median PFS for the lowest PD-L1 expression group (score 0) was 1.9 months for atezolizumab and 4.1 months for docetaxel (HR = 1.17; 95% CI, 0.72-1.82).

The trend continued with regard to objective response rates (ORR). In the tumor cell 3 or immune cell 3 group, atezolizumab yielded a 38% response rate compared with 13% for docetaxel. However, the rates were 8% for atezolizumab and 10% for docetaxel in the tumor cell 0 or immune cell 0 group. Overall ORR was 15% for both arms.

“The POPLAR phase 2 study demonstrated a pattern of improved survival that correlated with increasing PD-L1 expression,” Spira said. “A second randomized study in this patient population is ongoing.”

For more information:

Spira AI, et al. Abstract 8010. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

Disclosure: Spira reports receiving research funding from Roche Pharma. Please see the abstract for a full list of the other researchers’ relevant financial disclosures.

Perspective

Wallace Akerley, MD

Effective biologic therapies were promised to me when I was in medical school 30 years ago. Now, it is a reality. This randomized phase 2 study showed that the immune stimulator was easier to tolerate and achieved better survival.
The main point of this study, though, was to look at biomarkers. This drug is an anti–PD-L1 antibody, so for proof of principle, if the ligand wasn’t there, it was probably not going to work. When they looked at the stratified categories, if you had a little more of the biomarker, you did better. If you had a lot more of the biomarker, you did better still. The patients with the most biomarker did best. This is a dramatic improvement for this subset of patients.
This study does two things: It shows a proof of principle, and it shows that survival is improved with this therapy in patients with increasing levels of this biomarker. The gravy is that the toxicities were much easier to deal with. In many cases, patients don’t even know they are getting treated based on side effects.

Wallace Akerley, MD

Huntsman Cancer Institute

University of Utah

Disclosures: Akerley reports no relevant financial disclosures.

Perspective

Marina Chiara Garassino, MD

The intensity of PD-L1 and immune cells seems to correlate with outcomes for atezolizumab. We should celebrate because we have a new class of drugs for the treatment of non-squamous NSCLC. Results of the phase 2 trial of atezolizumab are promising.

Marina Chiara Garassino, MD

Fatebenefratelli and Ophthalmic Hospital

Disclosures: Garassino reports consultant/advisory roles with Bristol-Myers Squibb, Eli Lilly and Merck; research funding from AstraZeneca, Bristol-Myers Squibb, Merck and Roche; and travel expenses from Eli Lilly.