Frontline Nivolumab Approved by FDA for Advanced Melanoma

Nivolumab for Metastatic Renal Cell Carcinoma

Jeffrey S. Weber, MD, PhD

Nivolumab (Opdivo) has been approved by the FDA as a single-agent to include the frontline treatment of patients with BRAF wild-type advanced melanoma. This approval was based on a substantial improvement in overall survival (OS) compared with dacarbazine in a phase III study.

"Advanced melanoma continues to be one of the deadliest and most challenging cancers to treat, and ongoing research in Immuno-Oncology from clinical trials like CheckMate -066 shows the potential to provide improved overall survival for newly diagnosed patients with BRAF wild-type metastatic melanoma,” Jeffrey S. Weber, MD, PhD, deputy director of the Laura and Isaac Perlmutter Cancer Center at the NYU Langone Medical Center, said in a statement. “This important news means that we now have another new option to offer patients with BRAF wild-type metastatic melanoma.”

The CheckMate-066 trial consisted of 418 untreated patients, who were randomized in a 1:1 ratio to receive nivolumab at 3 mg/kg every 2 weeks (n = 210) or dacarbazine at 1000 mg/m2 every 3 weeks (n = 208). Of the patients enrolled, 61% had stage M1c disease and 36.6% had an elevated lactate dehydrogenase level.

The primary endpoint of the study was OS. Secondary endpoints included PFS, objective response rates (ORR), and quality of life.Data from the trial showed a median OS with nivolumab was not reached versus 10.8 months for dacarbazine, representing a 58% reduction in the risk of death (HR, 0.42; 95% CI, 0.30-0.60;P<.0001). Median progression-free survival (PFS) with nivolumab was 5.1 versus 2.2 months for dacarbazine (HR, 0.43; 95% CI, 0.34-0.56;P<.0001).

In updated data presented at the 2015 Society for Melanoma Research meeting, the 2-year OS rate with frontline nivolumab was 57.7% compared with 26.7% for dacarbazine. After a minimum follow-up of 15.1 months, median OS was not yet reached for patients receiving nivolumab compared with 11.2 months in the dacarbazine arm (HR, 0.43; 95% CI, 0.33-0.57;P<.001). The 1-year OS rates were 70.7% and 46.3%, for nivolumab and dacarbazine, respectively. Additionally, following progression in the dacarbazine arm, 13% of patients (n = 27) went on to receive nivolumab.

In the updated data, the median PFS was 5.4 months with nivolumab versus 2.2 months for dacarbazine (HR, 0.42; 95% CI, 0.32-0.53;P<.001). With nivolumab, the 1- and 2-year PFS rates were consistent, at 44.3% and 39.2%, respectively.

The ORR was 42.9% with nivolumab versus 14.4% with dacarbazine. A complete response was achieved by 11% of patients with nivolumab compared with 1% for dacarbazine. At the analysis, 81% of responses in the nivolumab arm remained ongoing.

All-grade adverse events (AEs) were similar between each arm but grade &ge;3 AEs were less common with nivolumab (13% vs 17%). The most frequently reported all-grade AEs in patients treated with nivolumab were pruritus (22%), diarrhea (18%), and rash (18%). Altogether, AEs led to discontinuation in just 6% of patients in the nivolumab arm.

"Our focused approach to Immuno-Oncology research is to deliver treatment options that have the potential to improve long-term survival outcomes for patients,&rdquo; Michael Giordano, MD, senior vice president, head of Oncology Development, Bristol-Myers Squibb, said in a statement. &ldquo;Opdivo has become a critical part of the treatment landscape for advanced melanoma patients and their physicians, both as a monotherapy and in combination, and we are committed to exploring opportunities for this treatment across stages of disease and lines of therapy.&rdquo;

Earlier this year, nivolumab was also approved in combination with ipilimumab for patients with advanced melanoma. A number of studies continue to assess nivolumab in various combinations for patients with melanoma and other types of cancer. A phase I/II study is looking at nivolumab with the anti-CD27 antibody varlilumab (NCT02335918). Additionally, a phase II/III study is exploring nivolumab and ipilimumab with the GM-CSF agent sargramostim (NCT02339571).

In addition to melanoma, the FDA has approved nivolumab as a treatment for patients with metastatic non-small cell lung cancer following a platinum-based chemotherapy regardless of histology or PD-L1 status and for patients with renal cell carcinoma following frontline antiangiogenic therapy. The frontline monotherapy indication marks the fifth approval for nivolumab.

Two-Year Survival and Safety Update in Patients (pts) with Treatment-Na&iuml;ve Advanced Melanoma (MEL) Receiving Nivolumab (NIVO) or Dacarbazine (DTIC) in CheckMate-066. Presented at the Society for Melanoma Research 2015 International Congress; November 18-21, 2015; San Francisco, CA.