Jason J. Luke, MD, FACP
Although nivolumab (Opdivo) and ipilimumab (Yervoy) together demonstrate superior survival in previously untreated patients with advanced melanoma, the combination comes with additional toxicity and an increased price tag, says Jason Luke, MD, assistant professor of Medicine at the University of Chicago Medicine.
“There have been several studies designed around trying to predict which patients are most likely to benefit from anti–PD-1 or immunotherapy combinations. I really think that is going to be an essential part of the future approach to treatment, says Luke. “Not all patients respond to these treatments. There are additional toxicities with the combinations, and there are also cost issues because of how catastrophically expensive these drugs are. We really need to know which patients are most likely to respond and which aren’t.”
The phase III CheckMate-067 trial found that, after 9 months of follow-up, the median progression-free survival (PFS) was 11.5 months with the combination of nivolumab and ipilimumab, 6.9 months for nivolumab monotherapy, and 2.9 months for single-agent ipilimumab. The combination reduced the risk of progression by 58% compared with ipilimumab (HR, 0.42; P
The ORR was 57.6% with the combination compared with 43.7% and 19% for single-agent nivolumab and ipilimumab, respectively. In the combination arm, the complete response rate was 11.5% versus 8.9% and 2.2% with single-agent nivolumab and ipilimumab.
All-grade adverse events (AEs) were 95.5% for the combination, 82.1% for nivolumab, and 86.2% for ipilimumab. Rates of treatment-related discontinuations with the combination and single-agent nivolumab and ipilimumab arms were 36.4%, 7.7%, and 14.8%, respectively.
The FDA granted an accelerated approval to the combination of nivolumab and ipilimumab as a treatment for patients with BRAF V600
wild-type unresectable or metastatic melanoma, based on findings from the phase II CheckMate-069 study.
A supplemental biologics license application was submitted for the combination, as well as single-agent nivolumab, for the frontline treatment of BRAF
-mutant advanced melanoma, based on the CheckMate-067 results. This application was granted a priority review, with a decision deadline of January 23, 2016.
To better understand which patients will benefit from nivolumab and ipilimumab as well as other immunotherapy combinations, biomarker development is critical, says Luke.
In an interview with OncLive
, Luke discusses potential new methods for determining prognostic markers and the challenges of balancing toxicity with efficacy in designing combination regimens.
OncLive: Are there specific approaches to identifying immunotherapy biomarkers that seem promising?
: Several recently presented studies examined the impact of tumor-infiltrating lymphocytes (TILs) as a prognostic marker for immunotherapy, as well as PD-L1. A lot of people are talking about that, and I think it is very important.