Ipilimumab was associated with long-term OS rates that plateaued after 3 years in patients with unresectable or metastatic melanoma, according to results from a pooled analysis of phase 2 and phase 3 trials.
“We observed an apparent plateau in the survival curve regardless of prior therapy, ipilimumab dose or treatment regimen,” Dirk Schadendorf, MD, of the department of dermatology at the University Hospital Essen, Germany, and colleagues wrote. “In all analyses, including those with OS data from patients in the expanded access treatment protocol, the survival curves seemed to consistently begin around year 3 and extended up to 10 years in some patients.”
Schadendorf and colleagues sought to provide an estimate of the long-term OS benefit associated with ipilimumab (Yervoy, Bristol-Myers Squibb), which was approved in 2011 for the treatment of unresectable or metastatic melanoma.
Researchers evaluated data from 1,861 patients with advanced melanoma who were enrolled in 10 prospective and two retrospective clinical trials. Approximately two-thirds (n = 1,257) of the patients had received prior treatment.
Most patients received ipilimumab at the 3-mg/kg approved dose (n = 965) or an investigational 10-mg/kg dose (n = 706). The remaining 190 patients received other doses.
Patients received ipilimumab at least every 3 weeks for up to four doses. Some of the studies allowed patients who achieved a confirmed objective response or stable disease for 3 or more months to receive ipilimumab maintenance therapy every 12 weeks.
The durations of median follow-up ranged from 9 to 15 months across the studies.
Median OS for the entire population was 11.4 months (95% CI, 10.7-12.1) and 3-year OS was 22% (95% CI, 20-24). Researchers noted 254 patients were still alive at least 3 years after starting ipilimumab, after which survival rates tended to plateau. The longest survival follow-up was 9.9 years.
Median OS was slightly higher among treatment-naive patients compared with previously treated patients (13.5 months vs. 10.7 months).
Results of a subset analysis indicated median OS was similar among patients who received 3-mg/kg doses (11.4 months), 10-mg/kg doses (11.1 months) and other doses (12.4 months).
Researchers also evaluated data from 2,985 patients who were treated on an expanded access protocol. Median OS in this cohort was 9.5 months (95% CI, 9-10), and researchers noted survival also plateaued after year 3 at 21%.
The researchers acknowledged several limitations in their study, including the lack of a control group, the inclusion of multiple studies with different patient populations, and that the studies were conducted in different eras spanning approximately 10 years.
“Considering the historic median OS of approximately 8 to 10 months and a 5-year survival rate of approximately 10% in advanced melanoma, the results presented herein are encouraging for patients diagnosed with this aggressive disease,” Schadendorf and colleagues concluded. “Future investigations will focus on approaches to increase the proportion of patients who experience long-term survival, including combination studies with other inhibitors of immune checkpoint pathways.”
Despite these favorable long-term outcomes, several key factors — such as cost and toxicity —were left unaddressed, Antoni Ribas, MD, PhD, of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, and Keith T. Flaherty, MD, of the Massachusetts General Hospital Cancer Center, wrote in an accompanying editorial.
“Despite all of the exciting developments in the treatment of melanoma and the evidence that the newly approved therapies are changing the natural history of this disease, we are still far from the goal of benefiting most patients over the long term,” Ribas and Flaherty wrote. “And costs are growing exponentially. Ipilimumab was the first agent to demonstrate an improvement in OS, a benefit that we now know can be sustained even when measured in years. We look forward to building on this success and continuing improvement in the long-term outcomes of patients with advanced melanoma.” – by Cameron Kelsall
Disclosure: The study was funded by Bristol-Myers Squibb. The researchers report various financial ties with Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Novartis and Roche. Ribas and Flaherty report consultant roles with and stock ownership in Amgen, Compugen, Flexus Biosciences, Genentech/Roche, GlaxoSmithKline, Kite Pharma, Merck and Novartis.