FDA Greenlights Nivolumab as an Adjuvant Melanoma Therapy

Yesterday, nivolumab (Opdivo) was granted regular approval for the treatment of patients with melanoma whose disease spread to the lymph nodes or those with metastatic disease who have undergone resection, according to a press release.

“Today’s approval builds on our leadership in melanoma, offering physicians a new option with the potential to change the course of the disease through earlier intervention. Opdivo is the first PD-1 inhibitor approved as an adjuvant treatment for any cancer,” Johanna Mercier, head, US Commercial, Bristol-Myers Squibb, said in a company press release. “Our decision to study Opdivo versus Yervoy — an established standard of care with a proven survival benefit – represents our relentless pursuit to bring more effective treatments to patients.”

The new approval was granted based on improvements in recurrence-free survival (RFS), demonstrated in the CHECKMATE-238 trial. Included in the trial were 906 patients with completely resected stage 3b/c or stage 4 melanoma.

Patients were randomized 1:1 to receive nivolumab 3-mg/kg every 2 weeks or ipilimumab (Yervoy) 10-mg/kg every 3 weeks for 4 doses, then every 12 weeks starting at week 24, according to the release.

The primary efficacy outcome was RFS, which was defined as the time between randomization and the first recurrence, new primary melanoma, or death, according to the FDA.

The investigators found that 34% of patients treated with nivolumab experienced recurrence or mortality compared with 45.5% of ipilimumab-treated patients.

However, the FDA noted that median RFS was not reached among either cohort.

Nivolumab is the first PD-1 inhibitor to demonstrate superiority to ipilimumab in this population, according to Bristol-Myers Squibb.

The median duration of nivolumab treatment was 11.5 months, with 74% of patients treated for longer than 6 months, according to the release. Only 9% of patients discontinued due to adverse events.

Common adverse events included fatigue, diarrhea, rash, musculoskeletal pain, pruritus, headache, nausea, upper respiratory infection, and abdominal pain. Common immune-mediated adverse reactions observed in the trial were rash, diarrhea/colitis, and hepatitis, according to the release.

For this indication, the FDA recommends nivolumab 240-mg infused over 60 minutes every 2 weeks until recurrence or toxicity for a maximum of 1 year, according to the release.

“Although there are approved therapies to help prevent melanoma recurrence, around seven out of 10 patients with stage III disease do not receive treatment following surgery,” said Valerie Guild, co-founder and president, AIM at Melanoma Foundation. “As an advocate, I have witnessed countless times the frustration and fear patients experience when their cancer returns — even after it was removed by surgery. Today’s approval offers new hope for people with melanoma that their disease may not come back.”

Currently, nivolumab is indicated to treat melanoma, non-small cell lung cancer, advanced renal cell carcinoma, classical non-Hodgkin lymphoma, squamous cell carcinoma of the head and neck, urothelial carcinoma, colorectal cancer, and hepatocellular carcinoma.