Neal E. Ready, MD, PhD: CheckMate 817 was a trial that was done to expand the use of nivolumab and ipilimumab in looking at different dosing regimens, and regimens that could be every 3 weeks rather than every 2 weeks, and to look at special populations. It was a large population of patients who were untreated and who received a standard dose of nivolumab and ipilimumab. That is providing useful information, understanding the dosing, other drugs, and how they combine.
There was also a cohort A1 that was done to look at special populations. And the special populations were patients who had either performance status 2, HIV, or hepatitis. The outcome for that cohort was interesting because there was a question, would it be effective? Would the nivolumab and ipilimumab combination be effective in these patients, and would the combination be tolerated, or would we see excess toxicity in these patients with poor performance status or specific comorbid medical problems?
The toxicity was remarkable in that it was no different than what we had seen in the large randomized trials of patients with performance status 0 or 1. We looked at the data for CheckMate 227, CheckMate 9LA, and CheckMate 568; the performance status 2 patients didn't seem to have any significant increase in toxicity for grade 3 and 4 toxicities or discontinuation of treatment compared with patients with good performance status. There were a substantial number of patients who had responses to the treatment and the responses were durable.
This was an important study looking at these special populations. I recently reviewed some of the literature, and there's truly little data for performance status 2 patients with immunotherapy. I was able to find 1 trial looking at pembrolizumab alone out of the United Kingdom that showed that pembrolizumab was tolerated and effective in this population. I couldn't find any data for chemotherapy plus I/O in the performance status 2 population, so this is some of the little data that we have really showing that a combination immunotherapy can be safe and effective in these special populations. That's useful for a practicing clinician.
Transcript Edited for Clarity