Nivolumab compared to chemotherapy in patients with advanced melanoma

The objective of this study was to evaluate the safety and effectiveness of nivolumab (Opdivo) as secondary treatment in advanced melanoma.

In the advanced stage of melanoma (stage III/IV), cancer spreads from the skin to other parts of the body. BRAF inhibitors and immunotherapy are the standard treatments for advanced melanoma. BRAF inhibitors are the drugs that stop / inhibit certain cell signaling proteins in melanoma cells containing mutations (permanent change) in the BRAF gene. This stops the growth of cancer cells. Immunotherapy uses the body’s own immune system to fight cancer. Nivolumab and ipilimumab (Yervoy) are examples of immunotherapy that works by inhibiting PD-1, an important protein in the immune system. This inhibition triggers the immune system to attack tumor cells and kill them.

However, for patients whose cancer progresses despite treatment with ipilimumab or a combination of ipilimumab and a BRAF inhibitor, further treatment options are currently limited. While previous studies have suggested that nivolumab has very promising outcomes in these types of patients, data is still quite limited.

In this phase III clinical trial, the effectiveness of nivolumab was compared with chemotherapy in advanced melanoma patients. All patients had progression of disease following previous treatment with ipilimumab or combination of ipilimumab and BRAF inhibitors.

Overall 631 patients from 14 countries were randomly assigned to receive either nivolumab or chemotherapy. Overall survival and the extent of tumor reduction were evaluated. Partial or complete decrease in tumor size was reported in 31.7% of patients in the nivolumab group compared to 10.6% in the chemotherapy group.

The average progression-free survival (time following treatment before the disease progressed) was 4.7 months for the nivolumab group and 4.2 months for the chemotherapy group. The 6-month progression-free survival was 48% in the nivolumab group and 34% in the chemotherapy group.

Adverse events associated with nivolumab were an elevated amount of lipase (a protein found in the pancreas), liver toxicity, anemia (low levels of red blood cells; 5%) and fatigue (1% in each category). For the chemotherapy group, adverse events included low white-blood cell count (cells of the immune system; 14%), low platelet count (a component of blood; 6%), and anemia. Serious drug-related adverse events were reported in 5% of nivolumab and 9% of chemotherapy-treated patients.

The authors concluded that compared to chemotherapy, nivolumab was more effective and a safer second-line of treatment in advanced melanoma patients who previously received ipilimumab or/and BRAF inhibitors.