NIVOLUMAB APPROVED BY EMA AS FIRST LINE TREATMENT FOR METASTATIC MELANOMA

The European Commission (EC) has approved the programmed-death (PD)-1 immune checkpoint inhibitor nivolumab (Opdivo, Bristol-Myers Squibb) for advanced unresectable or metastatic melanoma in adults, regardless of BRAF status, the manufacturer announced today.

Nivolumab is the only PD-1 immune checkpoint inhibitor to receive an accelerated assessment in Europe and is the first PD-1 inhibitor approved by the EC in any cancer, according to a news release.

Notably, the United States has not yet approved the drug for the first-line treatment of advanced disease.

Two pivotal phase 3 CheckMate trials (066 and 037) formed the basis of the EC approval of nivolumab.

CheckMate 066 was conducted in patients with previously untreated metastatic melanoma (and without BRAF mutations). The results showed a 1-year survival rate of 73% with nivolumabvs 42% with dacarbazine, with a hazard ratio of 0.42 (P < .0001). The most common treatment-related adverse events with nivolumab were fatigue (20%), pruritus (17%), and nausea (16.5%).

CheckMate 037 was conducted in patients with advanced melanoma who had been previously treated with and progressed while receiving ipilimumab (Yervoy, Bristol-Myers Squibb) and, if BRAF mutation-positive, a BRAF inhibitor.

A planned interim analysis showed an improvement in objective response rate of 32% with nivolumab vs 11% with chemotherapy (investigator's choice). A majority (87%) of patients had ongoing responses, with durability of response ranging from 2.6 to 10 months. Responses to nivolumab were seen in patients both with and without BRAF mutation and regardless of PD-L1 expression.

In this study, serious adverse reactions occurred in 41% of patients receiving nivolumab. Grade 3 and 4 adverse reactions occurred in 42% of patients, and the most frequent of these were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. The most common adverse reaction was rash (seen in 21% of patients).

The company also notes that nivolumab is associated with immune-mediated pneumonitis, colitis, hepatitis, nephritis and renal dysfunction, hypothyroidism and hyperthyroidism, and embryofetal toxicity.

According to the Bristol-Myers Squibb news release, "The incidence of melanoma has continued to increase in almost all European countries, with an estimated 1 in 5 patients expected to develop metastatic, or advanced, disease. Historically, prognosis for late-stage metastatic melanoma has been poor: the average survival rate for stage IV is just 6 months with a 1-year mortality rate of 75%."

Nivolumab is an "important step forward in offering a new option for advanced melanoma patients in the European Union, especially considering that long-term benefits have largely been elusive in this treatment category," Dirk Schadendorf, MD, professor, director and chair, Clinic for Dermatology, University Hospital, Essen, Germany, said in the release.

The US Food and Drug Administration (FDA) approved nivolumab in December 2014 for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation-positive, a BRAF inhibitor.

In March of this year, the US Food and Drug Administration cleared nivolumab for treatment of patients with metastatic squamous non-small cell lung cancer with progression on or after platinum-based chemotherapy.