Nivolumab's new FDA expanded approval putsthe drug in the frontline for all patients with advanced melanoma, which Jedd D. Wolchok, MD, PhD, says will be beneficial for patients.
Jedd D. Wolchok, MD, PhD
In early February, the FDA granted expanded approval to nivolumab (Opdivo) as both a single agent, as well as in combination with ipilimumab (Yervoy), for patients with melanoma exhibiting BRAF V600 mutations. This expansion puts nivolumab in the frontline for all patients with advanced melanoma, which Jedd D. Wolchok, MD, PhD, says will be beneficial for patients.
"The approval brings the combination regimen to approximately twice as many patients on-label, now that the BRAF status is no longer considered," said Wolchok, chief, Melanoma and Immunotherapeutics Service, Department of Medicine and Ludwig Center at Memorial Sloan Kettering Cancer Center, and lead investigator of the CheckMate-067 study, in an interview with Targeted Oncology.
The expansion, and subsequent approval, was based on the 3-arm CheckMate-067 study. The study showed that the dual checkpoint inhibitor combination reduced risk of progression by 58%, as compared with ipilimumab alone (HR, 0.42; P <.0001) in patients with advanced melanoma. Single-agent nivolumab reduced risk of progression by 43%, as compared with single-agent ipilimumab (HR, 0.57; P <.0001).
Wolchok says the fact that nivolumab came out on top as both a single-agent, as well as in combination, is beneficial to patients in that it offers yet another option in the malignancy's growing treatment paradigm. He added that the combination of nivolumab and ipilimumab produces significantly longer progression-free survival compared with ipilimumab alone.
"Fortunately, there are now numerous medications available for patients with metastatic melanoma harboring a BRAF V600 mutation. These include 2 different combinations of BRAF and MEK inhibitors, the nivolumab combination, monotherapy with each agent, and pembrolizumab monotherapy," he said.
The trial randomized 945 patients with untreated unresectable or metastatic melanoma to receive nivolumab (n = 316), ipilimumab (n = 315), or nivolumab plus ipilimumab followed by nivolumab (n = 314).
In the monotherapy arms, nivolumab was administered at 3 mg/kg every 2 weeks and ipilimumab was administered at 3 mg/kg every 3 weeks. In the combination arm, nivolumab at 1 mg/kg was administered with 3 mg/kg of ipilimumab every 3 weeks for 4 doses followed by 3 mg/kg of nivolumab every 2 weeks.
Patients were stratified by M-stage, PD-L1 status, and BRAF mutation status. Approximately one-third of patients were BRAF-mutation positive. The coprimary endpoints were progression-free survival (PFS) and overall survival, with objective response rate, safety, and other measures as secondary endpoints.
At more than 9 months of follow-up, the median PFS was 11.5 months for the combination, 6.9 months for nivolumab monotherapy, and 2.9 months for single-agent ipilimumab. Outcomes were similar regardless of BRAF mutation status.
Wolchok said while the combination has proven efficacious thus far, it does also come with its fair share of toxicities as compared with nivolumab as a single agent. These toxicities are largely reversible, he added, with the exception of endocrinopathies, which may require long-term hormone replacement.
In deciding if a patient should receieve either nivolumab as a single-agent, or in combination with ipilimumab, Wolchok said oncologists should carefully weigh their options.