Opdivo Granted Priority Review for Advanced Renal Cell Carcinoma

Opdivo shows extended overall survival and fewer adverse events in patients with RCC compared with Afinitor.

The FDA granted priority review designation to the PD-1 inhibitor nivolumab (Opdivo) for patients with advanced renal cell carcinoma (RCC) following prior antiangiogenic therapy.

The designation followed the results of the phase 3 CheckMate-025 trial that showed an extension in overall survival (OS). In the study, Opdivo was found to decrease the risk of death by 27% compared with everolimus (Afinitor), which represents a 5.4-month improvement in median OS.

Opdivo was previously granted breakthrough therapy designation in September 2015, with final approval for the supplemental biologics license application (sBLA) expected in March 2016.

“There remains a significant unmet medical need for advanced renal cell carcinoma patients who have received prior therapy and are often repeatedly treated with agents that are similar in mechanism," said Michael Giordano, MD, head of Oncology Development at Bristol-Myers Squibb, in a release. "We are pleased the FDA has accepted our sBLA for Opdivo in RCC, and we will continue to work with urgency to bring Opdivo to patients with this cancer.”

Opdivo was initially approved by the FDA in December 2014 for the treatment of unresectable or metastatic melanoma following treatment with ipilimumab (Yervoy) or a BRAF inhibitor.

The FDA recently approved the drug for patients with pretreated advanced non-small cell lung cancer across all histologies, in addition to approving the combination therapy of Opdivo and Yervoy for advanced melanoma.

The open-label CheckMate-025 trial enrolled 821 pretreated patients with a median age of 62 years who have advanced or metastatic clear-cell RCC and randomized them in a 1:1 ratio to receive either Opdivo or Afinitor.

Patients received Opdivo intravenously at 3 mg/kg every biweekly (n = 406), while Afinitor was administered orally at 10 mg (n = 397) per day. The primary endpoint of the trial was OS, while secondary outcome measures included objective response rate (ORR) and progression-free survival (PFS).

Among patients in the trial, 72% received 1 angiogenesis inhibitor and 28% received 2. At the minimum follow-up date of 14 months, median OS was 25 months in the Opdivo treatment arm compared with 19.6 months in the Afinitor arm (HR, 0.73; 98.5% CI, 0.57-0.93; P = .002).

The median PFS in patients treated with Opdivo was 4.6 months compared with 4.4 months in the Afinitor group (HR, 0.88; 95% CI, 0.75-1.03; P = .11).

A sensitivity analysis of patients who did not progress at 6 months showed median PFS at 15.6 months in the Opdivo group compared with 11.7 months in the Afinitor group (HR, 0.64; 95% CI, 0.47-0.88).

All-grade adverse events occurred in 79% of patients treated with Opdivo compared with 88% in the Afinitor group. Fatigue (33%), nausea (14%), and pruritus (14%) were the most frequently reported adverse events with Opdivo, while fatigue (34%), stomatitis (29%), and anemia (24%) were the most common adverse events in the Afinitor arm.

Grade 3/4 toxicities were found in 19% of patients treated with Opdivo compared with 37% of patients administered Afinitor. The most common grade 3/4 adverse events were fatigue (2%) in the Opdivo cohort and anemia (8%) in the Afinitor cohort, while there were 2 treatment-related deaths in the Afinitor group and none in the Opdivo group.