Nivolumab increases 5-year survival in metastatic melanoma

NEW ORLEANS — More than one-third of patients with heavily pretreated melanoma who received subsequent nivolumab therapy remained alive at 5 years, according to data presented at the American Association for Cancer Research Annual Meeting.

Perspective from Anthony J. Olszanski, MD, RPh

“This represents the longest follow-up to date for any anti–PD-1 treatment in any specific disease,” F. Stephen Hodi, MD, associate professor of medicine at Harvard Medical School and director of the Melanoma Center and Center for Immuno-Oncology at Dana-Farber Cancer Institute, said during a press conference. “The patients were heavily pretreated, receiving up to five lines of prior systemic therapies.”

F. Stephen Hodi

The results of an early phase 1 study by Topalian and colleagues showed patients with previously treated melanoma assigned nivolumab (Opdivo, Bristol-Myers Squibb) achieved durable tumor responses, even after discontinuation.

The current analysis included 107 patients (median age, 67 years; 67% men). Of these, 62% had received at least two prior systemic therapies.

Researchers assigned patients to 0.1- mg/kg, 0.3- mg/kg, 1- mg/kg, 3- mg/kg or 10-mg/kg doses of nivolumab every 2 weeks for up to 96 weeks. Investigators followed patients for OS, PFS, long-term safety and response after treatment discontinuation.

Treatment commenced in October 2008. The current data were analyzed in October 2015, with a minimum follow-up of 45 months.

Thirty-four percent (95% CI, 25-43) of the cohort achieved 60-month OS, and the median OS was 17.3 months (95% CI, 12.5-37.8). According to NCI SEER data, the 5-year survival rate for patients with metastatic melanoma diagnosed between 2005 and 2011 was 16.6%.

OS rates appeared to plateau around 48 months; however, additional follow-up is required to adequately observe the trend, Hodi said.

Patients assigned to nivolumab at the currently approved dose of 3 mg/kg (n = 17) experienced similar outcomes as the overall cohort (median OS, 20.3 months; 60-month OS, 35.3%).

Researchers reported a 30-month PFS rate of 18.6%. The 30-month PFS rate among patients assigned the currently approved dose was 25.7%.

The researchers permitted retreatment with nivolumab monotherapy in five patients. All patients had been off treatment for more than 100 days and resumed treatment at their originally assigned dose.

“All five patients regained disease control, and in all patients, the disease control was again durable,” Hodi said. “One patient had an adrenal metastasis removed, leaving him with no evidence of disease, which has led to a long-term durable benefit. This suggests the importance of the memory aspects of checkpoint blockade and its long-term adaptability.”

The most common adverse events across the entire cohort included fatigue (any grade, 29.9%; grade 3, 1.9%), rash (any grade, 23.4%; grade 3, 0%), diarrhea (any grade, 17.8%; grade 3, 1.9%), pruritus (any grade, 13.1%; grade 3, 0%) and nausea (any grade, 8.4%; grade 3, 0.9%).

“These data suggest durable, long-term survival with nivolumab monotherapy,” Hodi said. “The field of melanoma immunotherapy continues moving at lightning speed, and our hope and goal is to consider what the next steps are.” – by Cameron Kelsall

Reference:

Hodi FS, et al. Abstract CT001. Presented at: American Association for Cancer Research Annual Meeting; April 16-20, 2016; New Orleans.

Topalian SL, et al. J Clin Oncol. 2014;doi:10.1200/JCO.2013.53.0105

Disclosure: Bristol-Myers Squibb funded this study. Hodi reports research funding from and an unpaid consultant role with Bristol-Myers Squib.

Perspective

Anthony J. Olszanski, MD, RPh

Just 5 years ago, the outlook for patients with melanoma was quite poor, and no agent demonstrated a survival benefit to those patients with metastatic disease. The 5-year survival rate was below 10%. Ipilimumab (Yervoy, Bristol-Myers Squibb), a CTLA-4 inhibitor, changed this outlook, becoming the first agent to ever demonstrate a survival benefit. It also became apparent that some patients had remarkably durable responses, without evidence of new disease for years. In fact, the 5-year survival rate was 18.2%, with an apparent plateau at 3 years.

Two years ago, we witnessed the approval of the PD-1 inhibitors, which significantly enhanced the response rate, approximating 40% in patients with metastatic melanoma, and again demonstrated an OS benefit. Now we have evidence, again, of durable disease control. Remarkably, nivolumab (Opdivo, Bristol-Myers Squibb) has demonstrated a 5-year survival rate of 34% across a range of doses. With unfettered enthusiasm, we eagerly await maturation of combination trials, such as with ipilimumab and nivolumab, which have already demonstrated evidence of increase efficacy over single-agent therapy. Once a disease almost universally fatal, melanoma is clearly retreating from the advance of rational therapeutics, giving hope to thousands of patients each year.

Anthony J. Olszanski, MD, RPh

Fox Chase Cancer Center

Disclosures: Olszanski reports honoraria from and consultant roles with Bristol-Myers Squibb, Merck and Takeda Oncology.