Nivolumab Outperforms Investigator-Chosen Chemotherapy in Melanoma Trial

Nivolumab shows promise in patients whose disease progressed after ipilimumab and BRAF inhibitor therapy.

In the phase 3 CheckMate 037 trial, researchers reported the results of treatment with nivolumab (Opdivo) in patients with advanced melanoma who had previously experienced cancer progression after initial treatment with ipilimumab. Nivolumab, which works by inhibiting the programmed cell death receptor ligand checkpoint in tumor immune escape, offers an additional immunologic mechanism that is different from the CTLA-4 checkpoint inhibition offered by ipilimumab therapy.

Researchers evaluated the medication in patients age 18 years and older who had metastatic melanoma that progressed after either ipilimumab therapy or BRAF inhibitor therapy (provided they had the qualifying BRAF mutation). In addition, none of the trial participants were eligible for resection, typically due to the metastatic nature of the cancer.

One-third of patients received treatment with background therapy (dacarbazine/paclitaxel/carboplatin), and the remaining two-thirds received monotherapy with nivolumab 3 mg/kg administered every 2 weeks. Treatment continued until unacceptable toxicity or disease progression occurred.

Researchers assessed a primary end point of objective response and overall survival--more stringent than either end point used in isolation. Objective responses occurred in close to one-third of patients receiving nivolumab (31.7% of patients) versus just over 1 in 10 (10.6%) patients receiving traditional chemotherapeutic background therapy.

Patients receiving nivolumab experienced several grade 3 and grade 4 adverse events, including increased levels of lipase, increased levels of liver enzymes, anemia, fatigues, and neutropenia. Fortunately, rates of each of these adverse events did not exceed 1%. Blood dyscrasias also occurred in the standard treatment group, including neutropenia, thrombocytopenia, and anemia. These adverse events were far more common in patients receiving standard therapy, occurring in 5% to 14% of patients each.

Encouragingly, no treatment-related deaths were reported in the study.

Regarding these positive results, in a press release, Jeffrey S. Weber, MD, PhD, director of the Donald A. Adam Comprehensive Melanoma Research Center at Moffitt Cancer Center stated, “These data are important as they mark the first presentation of results from a Phase 3 randomized study for the PD-1 immune checkpoint inhibitor class.”

Nivolumab was approved by the FDA for the treatment of advanced melanoma on December 22, 2014. More recently, the medication received approval for use in non—small cell lung cancer.

“These results confirm our belief in the potential of immuno-oncology, and our broad development program continues to evaluate Opdivo in advanced melanoma across lines of therapy, both as a single agent and as part of a combination regimen,” said Senior Vice President and head of Oncology Development at Bristol-Myers Squibb, Michael Giordano, MD.

References

• Weber JS, D'Angelo SP, Minor D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015;16(4):375-384.
• Bristol-Myers Squibb. Positive Phase 3 Data for Opdivo (nivolumab) in Advanced Melanoma Patients Previously Treated with Yervoy (ipilimumab) Presented at the ESMO 2014 Congress; First Phase 3 Results Presented for a PD-1 Immune Checkpoint Inhibitor [press release]. http://news.bms.com/press-release/rd-news/positive-phase-3-data-opdivo-nivolumab-advanced-melanoma-patients-previously-t. Accessed July 2015.
• FDA. FDA approves Opdivo for advanced melanoma. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427716.htm. Accessed July 2015.
• OPDIVO (nivolumab) injection [package insert]. Princeton, NJ: Bristol-Myers Squibb; 2015.