Insights From: Hossein Borghaei, DO, Fox Chase Cancer Center; Corey J. Langer, MD, Perelman School of Medicine; Vassiliki Papadimitrakopoulou, MD, MD Anderson Cancer Center
Hossein Borghaei, DO: I think that in the up-front setting, the data are coming in fast and furious, but they’re welcomed data. They’re data that are showing improvement in overall survival. They’re data that are encouraging. They’re data that show a combination of chemotherapy plus an immuno-oncology drug, usually a PD-1 or PD-L1 antibody, is in fact a combination that can improve clinical efficacy. Moreover, it appears that the side effects are consistent with what we have been expecting or seeing from earlier studies.
I think the amount of data could be a little bit overwhelming: the rapidity with which everything is being released. But if you take a step back and look at the overall goals of the studies, you’ll see that it appears the combination of chemotherapy plus an I-O (immuno-oncology) agent is in fact a very active combination for the majority of patients who do not have a driver mutation adenocarcinoma. We’re hoping that the data about to come out will also show a similar pattern for patients with squamous cell carcinoma, but we don’t really have those data at this point.
Immuno-oncology combinations now come in a couple of different varieties. We have chemotherapy plus an immuno-oncology agent, and then we have at least 1 phase III study that has shown positive PFS, CheckMate-227, which is a combination of 2 different immuno-oncology drugs. The major issue with CheckMate-227 at this point is that the combination of ipilimumab and nivolumab is not an FDA-approved combination. The biomarker that was used in that study, tumor mutational burden, is also something that is not commonly used yet.
I think the I-O–I-O combination has a little bit of a challenge ahead of it right now, just because it’s not approved. On the other hand, a combination of pembrolizumab with carboplatin and pemetrexed has been approved for over a year now in the United States based on a phase II study. The pickup for that has been a little bit faster, and people have gravitated toward that even before the confirmatory KEYNOTE-189 phase III trial. I don’t think we’re done with I-O–I-O combinations. I don’t think we’re going to see anything new in the frontline setting for a while, but I think the push is there to come up with better I-O combinations to improve even further the current clinically efficacious combinations that we have.