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First-line atezolizumab plus chemotherapy improves PFS for lung cancer

Issue: October 25, 2018

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The addition of frontline atezolizumab to carboplatin or cisplatin plus pemetrexed improved PFS among patients with non-small cell lung cancer, according to interim results from a global phase 3 randomized trial presented at International Association for the Study of Lung Cancer’s World Conference on Lung Cancer.

IMpower132 is an open-label study of atezolizumab (Tecentriq, Genentech) — a PD-L1 inhibitor — among 578 chemotherapy-naive patients with stage IV nonsquamous NSCLC. Exclusion criteria included EGFR or ALK mutations, untreated central nervous system metastases, autoimmune disease and prior exposure to immunotherapy

Vassiliki A. Papadimitrakopoulou, MD, chief of the section of thoracic medical oncology at The University of Texas MD Anderson Cancer Center, and colleagues assigned half the patients to atezolizumab plus cisplatin or carboplatin and pemetrexed, followed by maintenance treatment with pemetrexed and atezolizumab. The other patients received chemotherapy alone with pemetrexed maintenance.

Investigator-assessed PFS using RECIST v1.1 and OS in the intention-to-treat population served as coprimary endpoints.

Results showed a 40% improvement in PFS among patients treated with the atezolizumab combination compared with those treated with chemotherapy alone (7.6 months vs. 5.2 months; HR = 0.6, 95% CI, 0.49-0.72).

The combination also improved PFS across key clinical subgroups, including among Asian patients (HR = 0.42; 95% CI, 0.28-0.63), those who never smoked (HR = 0.49; 95% CI, 0.28-0.87), and current and former smokers (HR = 0.61; 95% CI, 0.5-0.74).

Researchers observed a numerical but not statistically significant improvement of 4.5 months in median OS (18.1 months vs. 13.6 months; HR = 0.81, 95% CI, 0.64-1.03).

Final OS data are expected next year.

“The findings from IMpower132 indicate that the addition of atezolizumab to a backbone of carboplatin and pemetrexed chemotherapy provides better clinical efficacy than carboplatin and pemetrexed alone,” Papadimitrakopoulou said in a press release. “By inhibiting the interaction of PD-L1 with its receptors PD-1 and B7.1, atezolizumab restores tumor-specific T-cell immunity, offering a valuable treatment option that prolongs survival for patients with stage IV nonsquamous NSCLC.”

The objective response rate was 47% among patients treated with the atezolizumab combination compared with 32% in the control group.

Median duration of response was 10.1 months among the combination group compared with 7.2 months among those treated with chemotherapy alone.

The safety profile for the combination appeared consistent with the known safety profiles of the individual medicines. Researchers observed no new safety signals. Overall, 53.6% of patients treated with atezolizumab had grade 3 or grade 4 treatment-related events compared with 39.1% of people receiving chemotherapy alone.

“This is our third phase 3 trial in nonsquamous NSCLC demonstrating that a Tecentriq-based regimen can help reduce the risk of disease progression for people living with this disease,” Sandra Horning, MD, chief medical officer and head of global product development at Genentech, said in a company-issued press release. “We will discuss these results with health authorities globally.” – by Cassie Homer

Reference:

Papadimitrakopoulou V, et al. Abstract OA05.07. Presented at: International Association for the Study of Lung Cancer’s World Conference on Lung Cancer; Sept. 23-26, 2018; Toronto, Canada.

Disclosures: Papadimitrakopoulou reports speaker or advisory board roles with, or research funding from AbbVie, ACEA Biosciences, Arrys, Araxes Pharma, AstraZeneca, Bristol-Myers Squibb, Checkmate, Clovis Oncology, Eli Lilly, Genentech, Guardant Health, Incyte, Janssen Research Foundation, Loxo, Merck, Nektar Therapeutics, Novartis, Pfizer, Roche, Takeda Pharma and TRM Oncology. Please see the abstract for all other authors’ relevant financial disclosures.