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Combination Therapy Effective in First-Line Treatment of Metastatic NSCLC


The addition of a programmed death ligand 1 (PD-L1) inhibitor to standard chemotherapy as first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC) results in significantly longer overall survival (OS) and progression-free survival (PFS), according to a study published in The New England Journal of Medicine(online: April 16, 2018; doi:10.1056/NEJMoa1801005).

This study was also presented at the 2018 AACR Annual Meeting (April 14-18, 2018, Chicago, IL).

Platinum-based chemotherapy lacks targetable mutations for advanced NSCLC. Pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment in patients with a tumor proportion score for PD-L1 of 50% or greater. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response ad longer progression-free survival than chemotherapy alone in a phase II trial.

Leena Gandhi, MD, PhD, NYU Langhorne Health (New York, NY), and colleagues analyzed the addition of pembrolizumab to chemotherapy as first-line treatment for patients with NSCLC.

This double-blind, phase III trial included a total number of 616 patients with metastatic non-squamous NSCLC without sensitizing EGFR or ALK mutations who had received no previous treatment for metastatic disease. Researchers randomly assigned patients (2:1) to receive pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for four cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy. Crossover to pembrolizumab monotherapy was permitted among the patients in the placebo-combination group who had verified disease progression.

Authors of the study noted the primary endpoints were OS and PFS, as assessed by blinded, independent central radiologic review.

After a median follow-up of 10.5 months, the estimated rate of OS at 12 months was 69.2% in the pembrolizumab-combination group vs 49.4% in the placebo-combination group. Improvement in OS was seen across all PD-L1 categories that were evaluated. Median PFS was 8.8 months in the pembrolizumab-combination group and 4.9 months in the placebo-combination group.

Additionally, researchers acknowledged that adverse events of grade 3 or higher occurred in 67.2% of the patients in the pembrolizumab-combination group and in 65.8% of those in the placebo-combination group.

“In patients with previously untreated metastatic non-squamous NSCLC without EGFR or ALK mutation, the addition of pembrolizumab to standard chemotherapy of pemetrexed and a platinum-based drug resulted in significantly longer OS and PFS than chemotherapy alone,” authors concluded. “The survival benefit for pembrolizumab-combination therapy was observed across all categories of PD-L1 expression.”—Janelle Bradley


Click the link for more AACR 2018 coverage: AACR Annual Meeting 2018