Forty percent of patients with advanced melanoma achieved 3-year OS with pembrolizumab, according to long-term follow-up of the KEYNOTE-001 study scheduled for presentation at the ASCO Annual Meeting.
Patients derived benefit from pembrolizumab (Keytruda, Merck), regardless of prior treatment with ipilimumab (Yervoy, Bristol-Myers Squibb).
“These data confirm that pembrolizumab provides a long-term survival benefit for patients with advanced melanoma,” Caroline Robert, MD, PhD, head of the dermatology unit at Institute Gustave-Roussy in Paris, France, said in a press briefing. “The response rate contrasts with past results from patients with this disease. The data show durable responses in one third of patients, with complete durable responses that are visible after stopping treatment.”
Pembrolizumab received accelerated approval for advanced melanoma in September 2014 based on data from KEYNOTE-001. Data from KEYNOTE-002 also has shown that pembrolizumab prolongs PFS compared with chemotherapy, and in KEYNOTE-006, pembrolizumab demonstrated superior OS and PFS compared with ipilimumab for patients with advanced melanoma.
Prior to the approval of ipilimumab in 2011, median survival for advanced melanoma had been less than 1 year, Robert said.
Robert and colleagues conducted long-term follow-up of patients treated on the KEYNOTE-001 study to determine 3-year OS. The analysis included 655 patients — enrolled into ipilimumab-naive and -treated cohorts — assigned 2-mg/kg or 10-mg/kg doses of pembrolizumab every 3 weeks or 10 mg/kg every 2 weeks until intolerable toxicity, disease progression or investigator decision to stop treatment. Seventy-five percent of patients had received one more previous therapies and 52% had received ipilimumab.
Following pembrolizumab discontinuation, researchers followed up with patients every 3 months to assess OS.
Median follow up was 32 months (range, 24-46); all patients were followed for a minimum of 2 years.
Mean treatment duration was 11.3 months and 21% of patients continued pembrolizumab beyond the data cutoff date of Sept. 18, 2015.
Overall, 358 patients died. The 3-year OS rate was 40% and median OS was 23.8 months (95% CI, 20.2-29).
OS rates appeared similar across treatment regimens, with the highest median OS being 25.9 months (95% CI, 18.9-41.8) in the 10 mg/kg every 2 weeks cohort.
Rate of 3-year OS was 41% in both cohorts who had and had not previously received ipilimumab. However, 3-year OS was higher in treatment-naive patients (45%), for whom median OS was 32 months (95% CI, 27.1-not reached).
Ninety-five patients achieved a complete response, 61 of whom stopped treatment as a result. Response duration ranged from 17+ months to 43+ months.
Two patients experienced disease progression after stopping treatment, one of whom restarted treatment with pembrolizumab.
The safety profile of pembrolizumab appeared comparable to data from other studies. The most common adverse events included fatigue (40%), itchiness (28%) and rash (23%). Eight percent of patients discontinued treatment due to adverse events.
“Advanced melanoma is still a very challenging cancer, which is why it is so remarkable that such a large proportion of patients see a long-term survival benefit from this therapy,” Robert said in a press release. “The results of this study further demonstrates the potential for long-term benefit with pembrolizumab.” –by Nick Andrews
Robert C, et al. Abstract 9503. Presented at ASCO Annual Meeting; June 3-7, 2016; Chicago.
The study was funded by Merck. Robert reports consulting/advisory roles with Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Novartis and Roche. Please see the abstract for a list of all other researchers’ relevant financial disclosures.