The U.S. Food and Drug Administration has approved Opdivo (nivolumab) in combination with Yervoy (ipilimumab) for the treatment of patients with BRAF V600 wild-type and BRAF V600 mutation-positive unresectable or metastatic melanoma-expanding the original indication for the Opdivo-Yervoy combination regimen for the treatment of unresectable or metastatic melanoma to now include patients, regardless of BRAF mutational status. The FDA also expanded the approved use of single-agent Opdivo to include patients with previously untreated BRAF mutation-positive advanced melanoma.
Both new indications are approved under accelerated approval, and continued approval for each indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Opdivo in combination with Yervoy had been approved last year for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma (OT 11/10/15 issue). Opdivo has also previously been approved by the FDA for the treatment of previously untreated patients with BRAF V600 wild-type unresectable or metastatic melanoma (OT 1/10/16 issue).
Safety & Efficacy
Safety and efficacy for the Opdivo-Yervoy combination regimen were evaluated in the Phase III, double-blind, randomized CheckMate -067 study of 945 previously untreated patients with advanced melanoma, including both patients with BRAF V600 mutations and those with wild-type advanced melanoma (OT 8/25/15 issue). Patients were randomized to receive Opdivo plus Yervoy, Opdivo alone, or Yervoy alone. Median progression-free survival was 11.5 months for patients receiving the combination therapy, 6.9 months for patients receiving Opdivo alone, and 2.9 months for patients receiving Yervoy.
The most common adverse reactions leading to a discontinuation of the Opdivo-Yervoy combination regimen or of Opdivo monotherapy were diarrhea, increased ALT, increased AST, and pneumonitis-all occurring more frequently among the patients receiving the combination therapy. And the most frequent serious adverse reactions for the patients receiving the combination regimen, as well as for the patients receiving single-agent Opdivo were fatigue, rash, diarrhea, and nausea. Other common reactions included pyrexia, vomiting, and dyspnea.
Other Approved Uses
Opdivo is also approved for the treatment of patients with unresectable or metastatic melanoma who no longer respond to other drugs (OT 1/25/15 issue). Opdivo is also approved for the treatment of patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy (OT 1/25/15 issue); for the treatment of patients with metastatic non-squamous non-small cell lung cancer (NSCLC) that has progressed during or after platinum-based chemotherapy (OT 11/25/15 issue); and for the treatment of patients with squamous NSCLC that has progressed on or after platinum-based chemotherapy (OT 4/10/15 issue).
Opdivo is marketed by Bristol-Myers Squibb.
Clinical Quick Facts
Drug: Opdivo (nivolumab) plus Yervoy (ipilimumab) combination therapy; and Opdivo monotherapy
Approved Indication: Treatment of patients with BRAF V600 wild-type and BRAF V600 mutation-positive unresectable or metastatic melanoma (for both the combination regimen and Opdivo monotherapy)
Serious Side Effects: Diarrhea, increased ALT, increased AST, pneumonitis, fatigue, rash, and nausea (for both)
Common Side Effects: Pyrexia, vomiting, and dyspnea (for both)