The approval was based on a substantial improvement in overall survival (OS) in a phase 3 study.
The FDA has expanded the approval for single-agent Opdivo (nivolumab) to include the frontline treatment of patients with BRAF wild-type advanced melanoma, based on a substantial improvement in overall survival (OS) compared with the chemotherapy dacarbazine in a phase 3 study.
In the data assessed by the FDA from the CheckMate-066 trial, the median OS with Opdivo was not reached versus 10.8 months for dacarbazine, representing a 58 percent reduction in the risk of death. Median progression-free survival (PFS) with Opdivo was 5.1 versus 2.2 months for dacarbazine.
"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, 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.”
In the phase III trial, 418 untreated patients were randomized in a one-to-one ratio to receive Opdivo at 3 mg/kg every two weeks (210 patients) or dacarbazine at 1000 mg/m2 every three weeks (208 patients). Of the patients enrolled, 61 percent had stage M1c disease and 36.6 percent 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.
In updated data presented at the 2015 Society for Melanoma Research meeting, the two-year OS rate with frontline Opdivo was 57.7 percent compared with 26.7 percent for dacarbazine. After a minimum follow-up of 15.1 months, median OS was not yet reached for patients receiving Opdivo compared with 11.2 months in the dacarbazine arm. The one-year OS rates were 70.7 percent and 46.3 percent, for Opdivo and dacarbazine, respectively. Additionally, following progression in the dacarbazine arm, 13 percent of patients (27 patients) went on to receive Opdivo.
In the update data, the median PFS was 5.4 months with Opdivo versus 2.2 months for dacarbazine. With Opdivo, the one- and two-year PFS rates were consistent, at 44.3 percent and 39.2 percent, respectively.
The ORR was 42.9 percent with Opdivo versus 14.4 percent with dacarbazine. A complete response was achieved by 11 percent of patients with Opdivo compared with 1 percent for dacarbazine. At the analysis, 81 percent of responses in the Opdivo arm remained ongoing.
All-grade adverse events (AEs) were similar between each arm but AEs of at least grade 3 were less common with Opdivo (13 percent vs 17 percent). The most frequently reported all-grade AEs in patients treated with Opdivo were pruritus (22 percent), diarrhea (18 percent), and rash (18 percent). Altogether, AEs led to discontinuation in just 6 percent of patients in the Opdivo 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,” Michael Giordano, MD, senior vice president, head of Oncology Development, Bristol-Myers Squibb, said in a statement. “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.”
Earlier this year, Opdivo was also approved in combination with Yervoy (ipilimumab) for patients with advanced melanoma. A number of studies continue to assess Opdivo in various combinations for patients with melanoma and other types of cancer. A phase I/II study is looking at Opdivo with the anti-CD27 antibody varlilumab. Additionally, a phase 2/3 study is exploring Opdivo and Yervoy with the GM-CSF agent sargramostim.
In addition to melanoma, the FDA has approved Opdivo 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 Opdivo.
Two-Year Survival and Safety Update in Patients (pts) with Treatment-Naïve 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.