FDA Grants Priority Review to Opdivo for Kidney Cancer

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As part of this program, the FDA plans to take action on the drug's application within six months instead of the standard 10 months under regular review.

The FDA has assigned a priority review designation to the PD-1 inhibitor Opdivo (nivolumab) as a treatment for patients with advanced renal cell carcinoma (RCC) following prior antiangiogenic therapy, based on an extension in overall survival (OS) in the CheckMate-025 trial.

As part of this program, the FDA plans to take action on the drug's application within six months instead of the standard 10 months under regular review.

In the pivotal phase 3 study, Opdivo reduced the risk of death by 27 percent versus Afinitor (everolimus), representing a 5.4-month improvement in median OS. Grade 3/4 adverse events (AEs) were also lower with the PD-1 inhibitor compared with Afinitor, according to data published in The New England Journal of Medicine (NEJM).

The priority review follows a breakthrough therapy designation for Opdivo, which was granted by the FDA in September 2015. A decision on whether or not the drug will be approved will made by March 16, 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," Michael Giordano, senior vice president, head of Oncology Development, Bristol-Myers Squibb, said in a statement. "We are pleased the FDA has accepted our [supplemental biologics license application] for Opdivo in RCC, and we will continue to work with urgency to bring Opdivo to patients with this cancer.”

In the open-label CheckMate-025 trial, 821 pretreated patients with advanced or metastatic clear-cell RCC were randomized in a one-to-one ratio to Opdivo or Afinitor. Of randomized patients, 803 received treatment. Opdivo was administered intravenously at 3 mg/kg every two weeks (406 patients) and Afinitor was given orally at 10 mg daily (397 patients).

The median patient age was 62 years. Seventy-two percent of patients had received one angiogenesis inhibitor and 28 percent had received two. OS was the primary endpoint, with secondary outcome measures including objective response rate (ORR) and progression-free survival (PFS).

At a minimum follow-up of 14 months, the median OS was 25.0 months with Opdivo versus 19.6 months with Afinitor. The OS benefit was observed across patient subgroups, with the greatest improvement with Opdivo seen for those with a poor MSKCC prognostic score.

Median PFS was 4.6 and 4.4 months in the Opdivo and Afinitor arms, respectively. In an ad hoc sensitivity analysis of patients who had not progressed at six months, the median PFS was 15.6 months with Opdivo versus 11.7 months with Afinitor. This analysis was meant to take pseudoprogression into consideration.

ORR was 25 percent in the Opdivo arm versus 5 percent in the Afinitor group. The median duration of response was 12.0 months for both arms, and the median time to response was 3.5 and 3.7 months in the Opdivo and Afinitor arms, respectively.

PD-L1 expression was not found to significantly impact the efficacy of Opdivo. Among patients with PD-L1 expression at least 1 percent, median OS was 21.8 versus 18.8 months for Opdivo and Afinitor, respectively. In patients with PD-L1 expression less than or equal to 1 percent, median OS was 27.4 and 21.2 months in the two arms, respectively. Similar outcomes were observed when using a 5 percent threshold for PD-L1 expression status, although only a small number of patients were evaluable by this criterion.

All-grade AE rates occurred in 79 percent of patients treated with Opdivo versus 88 percent in the Afinitor group. Fatigue (33 percent), nausea (14 percent) and pruritus (14 percent) were the most frequently reported AEs with Opdivo. The most common AEs in the Afinitor arm were fatigue (34 percent), stomatitis (29 percent) and anemia (24 percent).

"[Opdivo] showed a favorable toxicity profile, with fewer grade 3 or 4 adverse events compared to [Afinitor]," lead author of the NEJM article Robert J. Motzer, medical oncologist, Memorial Sloan Kettering Cancer Center, told CURE. "One of the previous standouts for [Afinitor] as a popular treatment in kidney cancer was its favorable safety profile, so showing an improvement in the safety profile compared to [Afinitor] is really remarkable."

Opdivo was initially approved in December 2014 for patients with unresectable or metastatic melanoma following treatment with Yervoy (ipilimumab) or a BRAF inhibitor. Since this initially approval, the agent has gained a number of other indications. Recently, the FDA approved the PD-1 inhibitor as a treatment for patients with pretreated advanced non—small cell lung cancer across all histologies. Additionally, Opdivo has been approved in combination with Yervoy for advanced melanoma.

Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma [published online September 25, 2015]. N Engl J Med. 2015;373:1803-1813.