Nivolumab to Treat Advanced Melanoma

Chicago—After 2 years of treatment, 43% of patients with advanced melanoma who received nivolumab were alive, according to a phase 1 study. The 1-year overall survival rate was 62%, and median overall survival was 16.8 months. All patients had received prior therapies and had a poor disease prognosis.

Median overall survival for patients was approximately 16 months if they took vemurafenib, approximately 10 months if they received ipilimumab, and approximately 9 months if they were treated with chemotherapy. Two-year survival rates for ipilimumab in phase 2 and 3 trials ranged from 24% to 33%, according to Mario Sznol, MD, a study author who presented the data during an oral abstract session at the ASCO meeting.

“These survival data compare very favorably with historical controls,” Dr. Sznol said.

Results were also posted online in the New England Journal of Medicine [doi: 10.1056/NEJMoa1302369]. Bristol-Myers Squibb, the marketer of nivolumab, supported the trial.

Dr. Sznol said there are 3 ongoing phase 3 trials in patients with melanoma to confirm the efficacy of nivolumab, an intravenous drug that targets the PD-1 receptor. The drug had previously shown substantial activity in a phase 1 dose escalation/cohort expansion study of patients with melanoma, renal cell carcinoma, and non–small-cell lung cancer. The results presented at the ASCO meeting were an update of that study.

In this trial, 107 patients whose disease had worsened despite prior treatments received 5 different doses of nivolumab, which were administered every 2 weeks during an 8-week treatment cycle. The doses were 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.

Patients were at least 18 years of age, had received between 1 and 5 prior systemic treatment regimens, had an Eastern Cooperative Oncology Group performance status score between 0 and 2, and had adequate hematologic, hepatic, and renal function. Median age of patients was 61 years, 67% were male, and 66% received at least 2 prior therapies.

The overall objective response rate was 31% for all patients, and the median duration of response was 2 years. The authors defined response as a tumor shrinkage of at least 30%.

By week 8, 45% of patients showed evidence of response, according to Dr. Sznol. As of March 2013, 58% of responding patients continued to respond to the drug. In addition, another 11% of patients had stable disease or an unconventional response.

Of the 33 patients who responded to treatment, 17 stopped taking the drug for reasons other than disease progression, including completion of treatment. Of those 17 patients, 12 continued to respond for at least 4 months after they stopped taking the drug.

“You do not necessarily need to maintain these patients with drugs in order for their response to persist,” Dr. Sznol said.

The median progression-free survival was 3.7 months, which Dr. Sznol said was “not overly impressive.” However, he added that the progression-free survival rates at 1 year (36%) and 2 years (27%) were “impressive.”

For patients receiving 3 mg/kg of nivolumab, the dose chosen for analysis in phase 3 trials, the median overall survival was 20 months and the median progression-free survival was 9.7 months. The overall objective response rate for patients in the 3-mg/kg group was 41%.

Dr. Sznol said that the drug was “generally very well tolerated” and added that nivolumab “was one of the best tolerated drugs I have given in the clinic.” The most common adverse events were skin, gastrointestinal, endocrinopathies, and hepatic. Of the adverse events, only 5% were moderate or severe.