Opdivo Shows Survival Benefit in Patients with Mutation-Specific Advanced Melanoma

Patients with BRAF wild-type advanced melanoma saw a survival benefit after treatment with Opdivo (nivolumab) compared with the chemotherapy agent dacarbazine, according to follow-up data published in JAMA Oncology.

In the study, the researchers reported three-year follow-up data from the randomized, controlled, double-blind phase 3 CheckMate 066 trial — which randomized participants who had previously untreated BRAF wild-type stage 3 or stage 4 melanoma to receive either Opdivo (210 patients) or dacarbazine (208 patients).

Opdivo, a type of immunotherapy, binds to PD-1, which is a protein found on T cells. The drug is meant to block PD-1 and help the body’s immune system kill cancer cells.

Characteristics of patients in both groups were similar; most were men and in their sixties. However, a higher percentage of patients in the Opdivo group had an Eastern Cooperative Oncology Group performance status of zero, meaning they were fully active and able to carry on all pre-disease performance without restriction.

Overall survival was the primary endpoint, with progression-free survival and objective response, as well as tumor PD-L1 expression as a predictive biomarker of overall survival as secondary endpoints.

During three-plus years of follow-up, the researchers saw that more than half (51.2 percent) of patients who received Opdivo were alive at three years compared with 21.6 percent of patients who were treated with dacarbazine. The median overall survival was 37.5 months and 11.2 months, respectively.

“Collectively, our results showed durable responses and long-term survival with (Opdivo) monotherapy, with no new (side effects) developing at late time points,” the researchers wrote.

Complete and partial responses, respectively, were reported for 19 percent and 23.8 percent of patients in the Opdvio group compared with 1.4 percent and 13 percent of patients in the dacarbazine group.

The median progression-free survival, or the time during and after treatment where the cancer does not worsen, was 5.1 months in the Opdivo group compared with 2.2 months in the dacarbazine group. Three-year PFS was 32.2 percent and 2.9 percent, respectively.

“As of the data cutoff, 63.8 percent of patients in the Opdivo group had disease progression or had died compared with 82.7 percent of patients in the dacarbazine group,” wrote the researchers.

In the Opdivo group, grade 3/4 side effects were seen in 15 percent of patients and in 17.6 percent of patients in the dacarbazine group. Side effects such as colitis (inflammatory bowel disease), diarrhea, increased alanine aminotransferase levels (which is associated with liver damage) and pneumonitis led to discontinuation of treatment in 4.9 percent of patients in the Opdivo group. Whereas, 2 percent of patients in the dacarbarzine group discontinued treatment because of diarrhea.

“The results of this three-year follow-up analysis provided evidence for a durable survival benefit with (Opdivo alone) in patients with previously untreated BRAF wild-type advanced melanoma,” wrote researchers. “Improved rates of complete response and longer progression-free survival, as well as overall survival, demonstrated durable benefit with (Opdivo alone) beyond one year. Novel combinations under evaluation using anti—PD-1 therapies as the backbone have the potential to further improve outcomes in patients with advanced melanoma.”