D. Ross Camidge, MD, PhD
The use of single-agent immunotherapy and chemoimmunotherapy in patients with both nonsquamous and squamous non–small cell lung cancer (NSCLC) has been addressed in several clinical trials. However, the decision of whether to use a monotherapy or combination approach requires further investigation, said D. Ross Camidge, MD, PhD.
“We are entering a renaissance in terms of immunotherapy for NSCLC,” said Camidge. “This is not necessarily just because we have these drugs, but we have a better understanding that they don’t work in everybody and how we should use them.”
Data from the KEYNOTE-024 trial of frontline pembrolizumab (Keytruda), for example, indicated a 37% reduction in the risk of death in patients with metastatic NSCLC (HR, 0.63; 95% CI, 0.47-0.86; P
= .002). Median overall survival (OS) was 30.2 months with pembrolizumab versus 14.2 months with chemotherapy.1
In KEYNOTE-189, the frontline combination of pembrolizumab and chemotherapy was found to reduce the risk of death by more than 50% in patients with nonsquamous NSCLC. The estimated 12-month OS rate at a median follow-up of 10.5 months was 69.2% (95% CI, 64.1-73.8) and 49.4% (95% CI, 42.1-56.2) in the pembrolizumab/chemotherapy arm and control arm, respectively (HR, 0.49; 95% CI, 0.38-0.64; P
Following the results of KEYNOTE-024 and KEYNOTE-189, Camidge said that combinatorial biomarkers and corresponding enrichment strategies will better define patients who will benefit most from immunotherapeutic approaches, as not everyone should receive PD-1/PD-L1 inhibitors.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Advanced Non–Small Cell Lung Cancer, Camidge, professor, Division of Medical Oncology, Joyce Zeff Chair in Lung Cancer Research, School of Medicine, Division of Medical Oncology, University of Colorado, discussed the use of immunotherapy in patients with NSCLC.
OncLive: Can everyone with NSCLC benefit from immunotherapy?
We’re entering a renaissance in terms of immunotherapy for NSCLC. This is not necessarily just because we have these drugs, but we have a better understanding that they don’t work in everybody and [of] how we should use them. The whole “battleground” has moved to the first-line setting. We have the idea that by enriching for PD-L1, we can give pembrolizumab monotherapy. That was the KEYNOTE-024 study. In that study, enrichment meant a tumor proportion score (TPS) of 50% or greater, which is about 30% of lung cancer across all histologies.
Then we had the KEYNOTE-189 trial, which shook up [the landscape] a little bit. That trial compared carboplatin/ pemetrexed with or without pembrolizumab in the nonsquamous population. You could see that, regardless of PD-L1 level, patients seem to get benefit—though not [as much as they do] from the addition of pembrolizumab.
Now, everybody with nonsquamous [NSCLC] has a chemoimmunotherapy option. If you have a high TPS, you have both a chemoimmunotherapy option and an immunotherapy monotherapy option. One of the research questions is in that high TPS group. Which is the right one? Do [those patients] need chemotherapy? That will be answered in a study called INSIGNIA. That will be running over the next few years.
The other burning research questions are in KEYNOTE-024, in which they had enriched up to 30% of the population to say [that these are the patients] you can give pembrolizumab monotherapy to. Was that bar too high, or could there be benefit given we know that occasionally you can get responders at lower TPS? Is there a larger group that can receive an immunotherapy option alone? KEYNOTE-024 allowed people with 1% TPS or greater.
The headline was that the OS hazard ratio was better, but that is misleading. When you show greater than or equal to 1% TPS, you’re still including those people with high TPS. When you take those out and look at just the patients with 1% to 49% TPS, the OS hazard ratio was not statistically significant. We’re seeing that most of the benefit was driven by the patients with high TPS. For me, if a patient doesn’t have a high TPS, pembrolizumab monotherapy shouldn’t be an option unless they’re unfit for anything else. In that case, patients should probably have chemoimmunotherapy.