In a phase I study of nivolumab in patients with advanced, metastatic melanoma, 34% are still alive 5 years later, a survival rate twice what was typical when the study began in 2008.

More than a third of patients with metastatic melanoma who were treated with the immunotherapeutic nivolumab (Opdivo; Bristol-Myers Squibb) are still alive after 5 years, researchers reported April 17 at the American Association for Cancer Research Annual Meeting 2016 in New Orleans, LA. The latest follow-up data from a phase I trial launched in 2008 indicate that nivolumab's benefits can persist long after treatment ends.

“These data provide a foundation for establishing antiPD-1 therapy as another standard for melanoma patients, and hopefully this would translate to other cancer types as well,” said the trial's principal investigator, F. Stephen Hodi, MD, director of the Melanoma Center at Dana-Farber Cancer Institute in Boston, MA.

The FDA approved nivolumab for melanoma in 2014, and for lung cancer and renal cell carcinoma in 2015. An immune checkpoint inhibitor, the monoclonal antibody blocks PD-1, boosting the body's antitumor response.

The phase I study enrolled 107 patients with advanced melanoma who had received at least two previous therapies. Each patient received the drug for up to 96 weeks; some stopped treatment sooner due to adverse effects or because their tumors were completely eradicated. In early results, published in the Journal of Clinical Oncology in 2014, tumors shrank in 31% of the participants, and their estimated median duration of response was 2 years.

According to the new data, 34% of patients were still alive after 5 years. Overall survival began to plateau around 4 years, indicating that those who lived that long would likely continue to experience a durable response. Although the study had no control group, this survival rate is well above what was typical for patients with metastatic melanoma around the time of the study's start. According to the NCI's Surveillance, Epidemiology, and End Results Program, 5-year survival between 2005 and 2011 averaged 16.6%.

Hodi also reported on five patients who initially responded to the drug but suffered a recurrence after being off of it for at least 100 days. Each restarted treatment with nivolumab at their original dose, and all responded for at least 6 months, with one still experiencing a complete response nearly 2 years later.

What makes nivolumab and other immunotherapeutics so exciting is the durability of response, said Louis M. Weiner, MD, director of the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC, who moderated the press conference at which Hodi presented his results. Although chemotherapies and targeted therapies can control cancer, drug resistance is common and can emerge within weeks or months.

Several questions remain. For example, scientists are not certain whether using nivolumab in combination with the CTLA-4 inhibitor ipilimumab (Yervoy; Bristol-Myers Squibb), will further prolong survival. Data supporting this one–two punch aren't yet available, but Hodi predicted that pairing the drugs might lead to better survival rates than either alone.

It's also uncertain how nivolumab compares to another anti–PD-1 immunotherapeutic, pembrolizumab (Keytruda; Merck), for the treatment of melanoma, because the two have not been studied head to head, Hodi noted. –Amber Dance