BARCELONA — The addition of atezolizumab to chemotherapy extended OS among patients with stage IV squamous non-small cell lung cancer and PD-L1-high tumors, according to results of the phase 3 IMpower131 trial presented at International Association for the Study of Lung Cancer World Conference on Lung Cancer.
However, researchers did not observe a benefit of atezolizumab (Tecentriq, AstraZenca), an anti-PD-L1 therapy, in patients without high PD-L1 expression.
“This is a very important trial because it was conducted in a group of patients for whom we need additional therapies,” Federico Cappuzzo, MD, director of medical oncology and of the department of hematology and oncology at Azienda Unità Sanitaria Locale della Romagna-Ravenna in Italy, said during a press conference.
The IMpower131 trial included 1,021 patients with stage IV squamous NSCLC who were chemotherapy naive and had an ECOG performance status of 0 to 1. Researchers enrolled patients regardless of PD-L1 immunohistochemical status.
Researchers randomly assigned patients 1:1:1 to one of three arms: 1,200 mg atezolizumab every 3 weeks plus carboplatin area under the curve 6 and 200 mg/m2 paclitaxel followed by atezolizumab maintenance therapy (arm A); atezolizumab plus carboplatin and 100 mg/m2 nab-paclitaxel followed by atezolizumab maintenance therapy (arm B); or carboplatin and nab-paclitaxel followed by best supportive care (arm C). Patients received therapy until progressive disease or loss of clinical benefit.
Investigator-assessed PFS and OS in the intent-to-treat population served as the study’s co-primary endpoints. Secondary endpoints included PFS and OS in PD-L1 subgroups, overall response rate, duration of response and safety.
Researchers previously reported positive PFS data from the study; the current analysis focused on a comparison of OS in arm B (n = 343) vs. arm C (n = 340).
Final OS in the intent-to-treat population showed no difference in OS between arm B vs. arm C (14.2 months vs. 13.5 months; HR = 0.88; 95% CI, 0.73-1.05).
However, when researchers looked exclusively at patients with high-PD-L1 tumor expression — defined tumor cell 3 or immune cell 3 PD-L1 levels — the atezolizumab-chemotherapy combination conferred a median OS of 23.4 months compared with a median OS of 10.2 months in the chemotherapy-alone arm (HR = 0.48; 95% CI, 0.29-0.81).
Grade 3 to grade 4 adverse events occurred among 68% of patients in arm B, with 21% of patients experiencing serious adverse events, and 57.5% of patients in arm C, with a 10.5% rate of serious adverse events. Overall, researchers observed no new safety signals.
“Based on these data, we concluded that IMpower131 is a positive trial, with a significant improvement in PFS and a meaningful survival difference in the group of patients with strongly PD-L1-positive tumors,” Cappuzzo said. “These data clearly suggest that these patients specifically may benefit from the combination of chemotherapy and atezolizumab.” – by Alexandra Todak
Cappuzzo F, et al. Abstract OA14.02. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer; Sept. 7-10, 2019; Barcelona.
Disclosures: Cappuzzo reports speaker or advisory board roles with AstraZeneca, Bristol-Myers Squibb, Merck, Pfizer, Roche and Takeda. Please see the abstract for all other authors’ relevant financial disclosures.