Pembrolizumab Is Effective in Unresectable Melanoma, at 4-Year Follow-Up

After 4 years of follow-up, pembrolizumab demonstrated durable antitumor activity and improved outcomes over ipilimumab in advanced melanoma, according to results from the KEYNOTE-006 trial. The results (abstract 9503) were presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.

“The role of pembrolizumab in advanced melanoma is very well established. It has significantly improved the overall survival and the progression-free survival compared with ipilimumab in patients with advanced melanoma,” said Georgina V. Long, MD, PhD, of the University of Sydney in Australia.

The KEYNOTE-006 trial included 834 patients with unresectable stage III or IV melanoma. They were randomized to receive one of two schedules of pembrolizumab (556 patients in total), or to ipilimumab (278 patients). The median age was 62 years in both groups, and approximately 35% of the patients had received one prior therapy before entering the trial. About 80% of the cohort was programmed death ligand 1 (PD-L1)–positive.

After a median follow-up of 45.9 months, the median overall survival was 32.7 months with pembrolizumab, and 15.9 months with ipilimumab, for a hazard ratio (HR) of 0.73 (95% CI, 0.61–0.89). Only among patients who were treatment-naive, the median overall survival was 38.7 months and 17.1 months, respectively, for an HR of 0.73 (95% CI, 0.57–0.93).

Progression-free survival was also better with pembrolizumab, with a median of 8.3 months compared with 3.3 months with ipilimumab, for an HR of 0.56 (95% CI, 0.47–0.67). Again, this was similar in treatment-naive patients, with an HR of 0.54 (95% CI, 0.43–0.67).

The overall response rate was 42% with pembrolizumab and 17% with ipilimumab; there were 76 complete responses with pembrolizumab (14%), and 9 with ipilimumab (3%). The overall response rates in treatment-naive patients were similar, at 47% and 17%, respectively.

“With 4 years of follow-up, pembrolizumab continues to provide durable antitumor activity in both treatment-naive and treatment-experienced patients with advanced melanoma,” Long said, adding that “retreatment with pembrolizumab upon disease progression can provide additional antitumor activity.”

Douglas B. Johnson, MD, of the Vanderbilt Ingram Cancer Center in Nashville, was the discussant for the session, and he highlighted that the progression-free survival even after stopping therapy was still very high. “It would be very nice to be able to predict which patients don’t maintain durable responses,” he said, and added that there is some indication that using PET scans as a marker can be effective. “Two years or less is a reasonable treatment duration” with pembrolizumab, he said.