NSCLC: Immunotherapy Toxicity Management

Paul K. Paik, MD:In terms of the side effects that we might anticipate from the KEYNOTE-021 cohort G regimen of carboplatin/pemetrexed/pembrolizumab, the trial continued all of the standard-of-care things that we do for carboplatin/pemetrexed-based regimens in terms of antiemetic regimens that go around the carboplatin with dexamethasone and in terms of the use of B12 and folic acid as ways to mitigate side effects from pemetrexed. All of these things should be considered and continued with this regimen. The one thing, of course, that we have to be observant with that we didn’t really with chemotherapy by itself are the autoimmune side effects that emerge from something as simple as pruritus or a rash or hypothyroidism—which I think we’re all comfortable managing at this point—to more severe adverse events like pneumonitis, colitis, or very bad skin rashes, for example. It’s important to be observant that these issues may emerge, and because pembrolizumab is being given now in a maintenance setting also in the first-line setting, these are things that can emerge later on also. So, really recognizing the emergence of these things early on, stopping the drug early on, and then treating generally with steroids to try to clamp down on the autoimmune side effect event is an important corollary to the management of patients on the KEYNOTE-021 cohort G regimen.

KEYNOTE-021 cohort G was the tip of the iceberg in terms of chemotherapy and immunotherapy combinations. There will be trials that will be reading out fairly soon, some of these this year, including CheckMate-227, which is the ipilimumab/nivolumab in the up-front setting versus chemotherapy versus nivolumab trial. The top-line results for tumor mutation burden were just announced earlier this week as being positive, so we’re eager to see what those data look like. IMpower150 has read out, which was the randomized phase III trial of carboplatin/paclitaxel/bevacizumab with or without atezolizumab. IMpower132, which is another pemetrexed/carboplatin regimen with or without atezolizumab, is another ongoing regimen. And there is a whole slew of other squamous lung cancer—specific chemotherapy/I-O regimens that I myself have my eye on as someone who tends to specialize in that subgroup of patients. So, there’s very much more to come in a relatively short period of time.

Transcript edited for clarity.