NEW ORLEANS — Pembrolizumab conferred better outcomes than ipilimumab among patients with PD-L1–positive advanced melanoma, according to results of the KEYNOTE-006 trial presented at the American Association for Cancer Research Annual Meeting.
“Higher degree of PD-L1 positivity correlated with greater improvement in PFS, OS and objective response rate,” Matteo Carlino, MD, of Crown Princess Mary Cancer Centre and Westmead and Blacktown hospitals in Australia, and colleagues wrote.
The anti–PD-1 antibody pembrolizumab (Keytruda, Merck) and the anti–CTLA-4 antibody ipilimumab (Yervoy, Bristol-Myers Squibb) both have demonstrated efficacy in advanced melanoma.
The randomized KEYNOTE-006 trial included 834 patients with ipilimumab-naive disease. Researchers assigned patients 1:1:1 to one of three regimens: pembrolizumab 10 mg/kg every 2 weeks, pembrolizumab 10 mg/kg every 3 weeks, or four cycles of ipilimumab.
Previously reported results showed pembrolizumab significantly improved objective response rate (ORR), PFS and OS.
At AACR, Carlino provided efficacy data from a second interim analysis and also presented outcomes data based on PD-L1 expression.
The analysis included 821 evaluable patients, 671 (82%) of whom were PD-L1–positive.
Patients assigned pembrolizumab achieved longer PFS (P < .00001 for both doses), longer OS (P = .0005 for the every-2-week dose; P = .0036 for the every-3-week dose) and a higher ORR (P < .00003 for the every-2-week dose; P = .00001 for the every-3-week dose).
The combination conferred a greater survival benefit than ipilimumab overall, but the benefit was more pronounced among patients with PD-L1–positive tumors (HR for PFS = 0.52; 95% CI, 0.43-0.64; HR for OS = 0.56; 95% CI, 0.43-0.74) than those with PD-L1–negative tumors (HR for PFS = 0.83; 95% CI, 0.55-1.26; HR for OS = 0.94; 95% CI, 0.56-1.6).
“As evidenced by treatment effect in all groups, pembrolizumab monotherapy is appropriate in patients regardless of PD-L1 status,” Carlino and colleagues wrote. – by Mark Leiser
Carlino M, et al. Abstract CT004. Presented at: American Association for Cancer Research Annual Meeting; April 16-20, 2016; New Orleans.
Carlino reports honorary from or advisory roles with Amgen, Bristol-Myers Squibb, Merck Sharpe & Dohme and Novartis. Please see the full study for a list of all other researchers’ relevant financial disclosures.