More than 33% of patients with heavily pretreated advanced melanoma are still alive at 5 years after starting nivolumab (Opdivo) monotherapy, reported F. Stephen Hodi, Jr, MD, Director of the Melanoma Center, Dana-Farber Cancer Institute, Boston, at the 2016 American Association for Cancer Research (AACR) meeting. According to the National Cancer Institute’s SEER database, the 5-year survival rate for patients with metastatic melanoma diagnosed between 2005 and 2011 was 16.6%, and, historically, the median survival has been 11 months. “These data represent the longest survival follow-up of patients who received anti–PD-1 therapy in a clinical study, and suggest durable, long-term survival with nivolumab monotherapy,” said Dr Hodi. The data provide an additional paradigm shift for the treatment of advanced melanoma, he said, which should translate to other cancer types. Nivolumab is already approved by the FDA for the treatment of advanced melanoma, kidney cancer, and non–small-cell lung cancer. Dr Hodi provided an update to a phase 1 dose-escalation clinical trial known as CA209-003, which was initiated in 2008 and involved 107 patients with advanced melanoma who had received ≤5 previous treatments (excluding CTLA-4 or PD-1 inhibitor), and who had received 1 of 5 doses of nivolumab (0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, or 10 mg/kg) every 2 weeks for up to 2 years. Treatment continued for up to 96 weeks. The updated safety and survival data presented at this AACR annual meeting were from a minimum follow-up of 45 months from the time of the first nivolumab dosing. The patients’ median age was 61 years, 67% of the patients were male, and 65% had received previous immunotherapy. The 5-year overall survival (OS) rate was 34%, with a median OS of 17.3 months among all patients, and a median OS of 20.3 months in the 3-mg/kg arm; in this arm, the 12-month survival was 64.7%, which declined incrementally at 24 months (47.1%), 36 months (41.2%), and 48 months (35.3%). The OS appeared to plateau at 48 months, “which is indicative of long-term benefit in some patients, although more follow-up is needed to fully appreciate the benefit of nivolumab monotherapy,” said Dr Hodi. An updated analysis of retreated patients showed that disease control was maintained, Dr Hodi said. The patients were permitted to receive retreatment with nivolumab under certain circumstances, which included experiencing progressive disease without dose-limiting toxicity after achieving disease control, not reaching 1-year follow-up without progressive disease, or not having already received retreatment. Overall, 5 patients were retreated at the same dose as originally assigned, after not receiving treatment for ≥100 days. At 30 months, the progression-free survival rates were 25.7% among patients assigned to nivolumab 3 mg/kg, and 18.6% for the entire cohort. Nivolumab continued to be safe and tolerable, with no deaths or new safety signals. The combination of ipilimumab (Yervoy) and nivolumab was approved by the FDA on September 30, 2015, for the treatment of patients with unresectable or metastatic melanoma without the BRAF V600 gene mutation. On January 23, 2016, this indication was expanded to include patients with unresectable or metastatic melanoma regardless of BRAFV600 mutation status; this most recent indication was based on findings from the CheckMate-067 clinical trial.