Long-term outcomes for nivolumab in patients with BRAF-negative advanced melanoma

This study investigated the long-term effectiveness and safety of immunotherapy drug nivolumab (Opdivo) compared to chemotherapy drug dacarbazine (DTIC-Dome) for patients with BRAF-negative advanced melanoma.

The study showed that nivolumab significantly increased survival in these patients.

Most melanoma tumors grow in response to an abnormality (mutation) to a gene called BRAF. This gene abnormality causes cancer cells to grow uncontrollably. These melanomas can be treated with targeted therapy that blocks BRAF mutations.

In BRAF-negative melanoma, no gene mutation of the BRAF gene was detected. Therefore, BRAF inhibitor drugs are not effective, therefore not recommended. Standard therapy for BRAF-negative melanoma included chemotherapy such as dacarbazine.

Immunotherapies such as nivolumab have become important treatment options. They help the body’s immune system recognize and kill the cancer cells. Previous data suggests significantly higher effectiveness of nivolumab over dacarbazine in a 3-year analysis in patients with BRAF-negative melanoma. However, the long-term effectiveness and safety of nivolumab in these patients is still unknown. 

This study included 418 patients with BRAF-negative, stage III-IV that could not be surgically removed. The patients were randomly placed in two groups. 210 patients received nivolumab and 208 patients received dacarbazine. Patients were followed up for at least 60 months.

Of patients receiving nivolumab, 39% were alive after 5 years, compared to 17% in the dacarbazine-group. The average survival time with nivolumab was 37.3 months compared to 11.2 months for dacarbazine. Nivolumab was associated with a 50% lower risk of mortality at 5 years compared to dacarbazine.

28% of the nivolumab-group were alive without cancer progression at 5 years, compared to 3% in the dacarbazine-group. 42% of the nivolumab-group and 14% of the dacarbazine-group responded to treatment. Of the 42 (20%) patients who had a complete response (disappearance of cancer signs) to nivolumab, 88% were alive at 5 years. 55% of the 47 patients who had a partial response to nivolumab were alive at 5 years.

Among the 75 patients on nivolumab who were alive at 5 years, 83% did not need further therapy. 60% of these patients were treatment-free. Severe side-effects appeared in 16% of patients taking nivolumab and 18% of patients taking dacarbazine. No new safety problems were reported.

The authors found that nivolumab showed significantly longer survival rates and durable response rates in patients with BRAF-negative advanced melanoma.

The study was supported by the pharmaceutical company Bristol Myers Squibb, the manufacturer of nivolumab.