More than one-third of patients with advanced melanoma were still alive 5 years after starting treatment with the anti-PD-1 immunotherapy nivolumab, according to long-term phase I data presented Sunday at the 2016 American Association for Cancer Research (AACR) Annual Meeting, held April 16–20 in New Orleans.
“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 F. Stephen Hodi, MD, director of the Melanoma Center at Dana-Farber Cancer Institute, associate professor of medicine and investigator at the Ludwig Center at Harvard Medical School, in a press conference ahead of the meeting.
Nivolumab is an immune checkpoint inhibitor that blocks PD-1 to enhance antitumor responses. It is currently approved as a first-line monotherapy in advanced melanoma, and in combination with ipilimumab.
At the meeting, Hodi presented data on the 5-year overall survival rates of a group of 107 patients with advanced melanoma from the CA209-003 study. All patients in the study had never been treated with ipilimumab and had received between one and five prior therapies for their disease. Patients were treated with nivolumab at one of five doses (0.1, 0.3, 1, 3, or 10 mg/kg) every 2 weeks for up to 2 years.
Among all patients, the 5-year overall survival was 34% (95% CI, 25%–43%). The median overall survival was 17.3 months (95% CI, 12.5–37.8) among all study patients and was 20.3 months for those who received the 3 mg/kg dose, the currently approved monotherapy dose.
At 12 months, the overall survival in patients who received 3 mg/kg nivolumab was 64.7%, which decreased to 47.1% at 2 years, 41.2% at 3 years, and 35.3% at 4 years, after which the survival rate plateaued.
At the last time-point for tumor assessment, the researchers found a progression-free survival of 18.6% for all patients on the trial, and 25.7% for patients assigned 3 mg/kg.
Some patients in the trial were permitted to be retreated with nivolumab monotherapy under specific conditions. This included patients who achieved disease control and subsequently went on to develop progressive disease but did not experience a dose-limiting toxicity prior to pretreatment. These patients also did not reach the 1-year follow-up without progressive disease, or had not already undergone retreatment.
According to Hodi, five patients in the study were treated at the same dose originally assigned to after coming off treatment for more than 100 days. In all five patients disease control was obtained again and was durable.
Nivolumab monotherapy continued to be safe, with no deaths or new safety signals.
This study was funded by Bristol-Myers Squibb.