Evidence for Immunotherapy in Frontline NSCLC

Benjamin P. Levy, MD: The KEYNOTE-189 study is practice-changing. This was a trial that looked at adding pembrolizumab to carboplatin/pemetrexed versus carboplatin/pemetrexed for patients with advanced nonsquamous non—small cell lung cancer. There has been a lot of evidence that suggest that immunotherapy works as a single-agent drug in the second-line setting for adenocarcinoma. This moved it up into the frontline setting. This was a very clean study, and the results were surprising. Patients in the triplet arm—carboplatin, pemetrexed, pembrolizumab—had improvements in response rate and progression-free survival. And importantly, they had a meaningful improvement in overall survival no matter what their PD-L1 level was.

The high PD-L1 expressors derived more meaningful benefits, but even in the patients with a PD-L1 level of less than 50%, there was a benefit in terms of progression-free survival and overall survival.

I think this triplet therapy, based on these results, has changed the way that we think about lung cancer and the way that we treat it. I would argue that every patient who has advanced adenocarcinoma, who does not have an actionable mutation, like EGFR or ALK, should be considered for the triplet therapy regimen.

It’s hard for me to believe that an FDA-approved regimen with carboplatin, pemetrexed, and pembrolizumab won’t change the way that the NCCN thinks about using these drugs. It’s very hard to argue with this data right now. It was surprising for us to see. This kind of runs against what we’re trying to do with precision medicine. We’re just adding a drug to a platinum-doublet, comparing it to a platinum-doublet, alone. But when you see this robust of a benefit, it’s hard to ignore. I think the NCCN will certainly adopt this regimen.