Discontinuation Did Not Reduce CheckMate 9LA Regimen’s Efficacy in NSCLC
David P. Carbone, MD, PhD, discusses the outcomes of the phase 3 CheckMate 9LA trial in non–small cell lung cancer based on treatment discontinuation.
David P. Carbone, MD, PhD, the Barbara J. Bonner Chair in Lung Cancer Research and director of the James Thoracic Center at The Ohio State University Comprehensive Cancer Center, discusses the outcomes of the phase 3 CheckMate 9LA trial (NCT03215706) in non–small cell lung cancer (NSCLC) based on treatment discontinuation.
The trial randomly assigned patients to receive nivolumab (Opdivo), ipilimumab (Yervoy), and 2 cycles of chemotherapy vs 4 cycles of chemotherapy. Some patients discontinued part or all of the regimen early due to toxicity concerns with the combination of nivolumab and ipilimumab given long term. Carbone notes that we know using a single PD-1 inhibitor has been efficacious in NSCLC. Additionally, a limited number of doses of ipilimumab are given when the combination is used in melanoma.
In an exploratory analysis, the patients who discontinued all components of treatment had a 5-year overall survival rate of 37% compared with only 20% in the full intent-to-treat (ITT) population. Carbone says that this shows that the immune-related adverse events [irAEs] with this regimen can be a significant concern, but they can be managed appropriately, and patients can still achieve benefit from treatment even if they discontinue drugs early due to toxicity.
TRANSCRIPTION:
0:10 | The other interesting analysis that's come out of that study was since the ipilimumab/nivolumab combination is more toxic than pembrolizumab [Keytruda] monotherapy, many patients end up stopping the ipilimumab and continuing the nivolumab. And in fact, in melanoma regimens, they don't continue the ipilimumab indefinitely, and that combination is clearly toxic, and anybody who's used the regimen shows that. But in an analysis of the [CheckMate] 9LA data, they look at patients who discontinued therapy, any part of the therapy, due to immune-related adverse events, what the survival of that subgroup was compared to the ITT population.
1:00 | It turns out that that population has an even better survival than the total ITT population. So in the 4-year analysis, it is about 40%. I think in the 5-year analysis, it was 37%.... So it's still pretty good compared to the 20% 5-year survival in the entire population. So that really tells you that concern about the immune-related adverse events is real, but that if it's managed appropriately—and one of the management approaches is to stop the ipilimumab and continue the nivolumab—if you do that, you're not negatively impacting patient outcomes, that those patients do fine.
