Moving to First-line

The use of these checkpoint inhibitors is being explored in other lung cancer settings, but 1 of the largest areas of interest is in moving these drugs into the first-line setting, according to Dr Gainor. Among the most eagerly awaited clinical trial results of the next year or 2 are the results of CheckMate 026 ( Identifier: NCT02041533) and KEYNOTE-024 ( Identifier: NCT02142738), which are comparing PD-1/PD-L1 inhibitors to platinum-based chemotherapy in treatment-naive populations.

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In June, Merck announced that the phase 3 KEYNOTE-024 trial demonstrated that pembrolizumab significantly improved progression-free and overall survival, in contrast with chemotherapy, among patients with treatment-naive advanced NSCLC that expressed PD-L1 at a rate of 50% or greater.2

In August, however, Bristol-Myers Squibb announced that its phase 3 CheckMate 026 did not meet its primary endpoint of progression-free survival among patients with previously untreated advanced NSCLC. This trial included patients whose tumors expressed PD-L1 at a rate of 5%.

“Of the 4 randomized controls trials of these drugs that showed overall survival benefits, only 1 in 4 showed a progression-free survival advantage,” Dr Gainor said. “When you go into the first-line setting, you are competing against a higher bar and against crossover, where all patients will receive PD-1 inhibitors in the second-line setting, so it will be difficult to see an overall survival benefit; researchers instead have to rely on differences in progression-free survival.”

Dr Gainor added, however, that progression-free survival may not be a good endpoint for these drugs, and that studies may have to stop looking at median survival, and instead focus on the entire survival curve or on hazard ratios and landmark analyses.

Full results of both trials are expected in the coming year.

Disclosures: Dr Gainor has a consulting/advisory relationship with Novartis, Bristol-Myers Squibb, Genentech/Roche, Clovis, Boehringer-Ingelheim, and has received honoraria from Merck.  

The author has no disclosures to report.


  1. Herzberg B, Campo MJ, Gainor JF. Immune checkpoint inhibitors in non-small cell lung cancer. Oncologist. 2016 Aug 17. doi: 10.1634/theoncologist.2016-0189 [Epub ahead of print]
  2. Merck’s KEYTRUDA (pembrolizumab) demonstrates superior progression-free and overall survival compared to chemotherapy as first-line treatment in patients with advanced non-small cell lung cancer [press release]. BusinessWire website. Updated June 16, 2016. Accessed August 29, 2016.
  3. Bristol-Myers Squibb announces top-line results from CheckMate -026, a phase 3 study of Opdivo (nivolumab) in treatment-naive patients with advanced non-small cell lung cancer [press release]. Bristol-Myers Squibb website.–026-a-Phase-3-Study-of-Opdivo-nivolumab-in-Treatment-Nave-Patients-with-Advanced-Non-Small-Cell-Lung-Cancer/default.aspx. Updated August 5, 2016. Accessed August 29, 2016.