Down the Keyhole.

Top Line: How much PD-L1 expression is needed to get pembro first-line for metastatic non-squamous cell (SCC) non-small cell lung cancer (NSCLC)?
The Study: We easily could have read this wrong but as far as we can tell, in the NCCN confusion-lines for metastatic NSCLC, patients that don’t have EGFR, ALK, ROS1, or BRAF mutations but who do have >50% PD-L1 expression get pembrolizumab. That isn’t many people. So what do we do with those who don’t have any of these mutations nor heavy PD-L1 expression? Regular. Old. Chemo. In KEYNOTE-189, this precise group of patients was randomized to platinum/pemetrexed x 4 cycles → pemetrexed maintenance +/- pembro throughout. The addition of pembro resulted in a substantial improvement in overall survival at 12 months (49→69%) with benefits falling nicely along the spectrum of PD-L1 expression: 10% for PD-L1 <1%, 20% for PD-L1 1-50%, and 25% for PD-L1 >50%. Of note, these results came with little to no additional toxicity. This is all pretty important because it moves pembro to the front-line setting for metastatic NSCLC regardless of PD-L1 expression, at least for non-mutated adenocarcinomas. The obvious next question: is chemo even needed at all? KEYNOTE-024 suggests not, particularly if PD-L1 is >50%.
Bottom Line: Adding pembro to platinum/pemetrexed combo chemo for non-mutated, non-SCC, metastatic NSCLC improves overall survival regardless of PD-L1 expression. | Gandhi, N Engl J Med 2018


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