Matthew D. Hellmann, MD
There are limited options for patients with small cell lung cancer after first-line platinum-based chemotherapy. In a search for treatment, researchers designed the CheckMate-032 trial to evaluate multiple regimens of nivolumab (Opdivo) plus ipilimumab (Yervoy), which showed signs of tolerability and efficacy.
The led to an expansion cohort, the first report of which was presented at this year’s ASCO annual meeting. Updated safety and efficacy findings showed that responses to nivolumab and nivolumab plus ipilimumab were durable, regardless of PD-L1 expression.
In an interview with OncLive
, lead author Mathew D. Hellmann, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discussed the first report of the randomized expansion cohort from CheckMate-032.
OncLive: Please provide an overview of the study.
CheckMate-032 was a phase I/II study of patients with small cell lung cancer who were treated with nivolumab with or without ipilimumab. The reason for the study was that, unfortunately, outcomes and treatment options for patients with small cell lung cancer are poor and new treatment options are desperately needed. There was an initial cohort of patients in this study of about 150 patients with small cell lung cancer who are were assigned to receive nivolumab or ipilimumab, and there were some early signs promising of efficacy. And as a result of that initial study, nivolumab with or without ipilimumab was added to the NCCN guidelines last year.
It also prompted a randomized study that we presented at ASCO for the first time, in which about 250 patients were randomized to either nivolumab or nivolumab with ipilimumab. This was to confirm efficacy and examine potential biomarkers that may be associated with response.
Our presentation ultimately came in 3 different parts. The first part was an update from the nonrandomized cohort, in which we used the previous data along with 6 months of additional follow-up. And it included, for the first time, an assessment of response by blinded independent review of the CT scans. In the second part, we presented the initial efficacy data from the randomized cohort—about 250 patients. And in the third part of the study, we combined the randomized and the nonrandomized patients into a total group of about 400 patients with small cell lung cancer to examine subgroup analysis and safety across the entire cohort.
What were the findings?
In the first part of the presentation, we examined the updated response data for patients in the nonrandomized cohort. In this part of the study, about 150 patients were assigned to received nivolumab or nivolumab plus ipilimumab. Using the blinded independent review scans, the response rate of nivolumab plus ipilimumab was 23% compared to 11% for patients who received nivolumab.
In contrast to other diseases, in small cell lung cancer, PD-L1 expression seems to be very uncommon and not predictive of response. There is actually a [greater] numerical increase in response rate in patients who were PD-L1–negative than those who were PD-L1–positive. It doesn’t seem that PD-L1 is an important biomarker for response in this disease.
Building on that initial efficacy, we then extended the survival analysis to examine longer term outcomes and found that 2-year estimated survival of patients treated with nivolumab plus ipilimumab was 26% compared to 14% in those who received nivolumab. Those sort of long-term survival numbers are generally not possible in this disease, which is rapidly progressive and rarely sees patients survive to 2 years. I think it is indicative of the long-term benefit that is possible in the subgroup of patients who really benefit from immunotherapy.
We next moved to the randomized portion of the study in which about 250 patients were randomized to receive nivolumab or nivolumab plus ipilimumab. This is the first time this data has been presented, and as a result, the outcomes are premature and follow-up is not long. But the response rate was the main part of this presentation. In the randomized cohort the response rate to nivolumab plus ipilimumab was 21% compared to 12% with nivolumab monotherapy. So, those response rates were very similar to what was seen in the earlier part of the study, and confirm that this efficacy that we are seeing seems to be real, even in a randomized setting.
The next major part of the presentation related to the pooled analysis of all 401 patients who were treated in both the randomized and nonrandomized parts of the study. We found that responses were seen in both second line, third line, and beyond. And responses were seen in platinum-sensitive and platinum-refractory patients. These sorts of immunotherapy can be beneficial for patients in a variety of settings, and platinum sensitivity did not seem to determine response.