PD-L1 Positivity Associated With Improved Efficacy of Pembrolizumab vs Ipilimumab

Programmed death-ligand 1 (PD-L1) positivity is associated with improved efficacy with pembrolizumab compared with ipilimumab in patients with advanced melanoma, a study presented at the American Academy for Cancer Research (AACR) Annual Meeting 2016 has shown.¹

Both the anti-PD-1 monoclonal antibody pembrolizumab and the anti-CTLA-4 antibody ipilimumab have demonstrated efficacy in advanced melanoma, but the KEYNOTE-006 trial showed that pembrolizumab significantly improved progression-free survival, objective response rate, and overall survival compared with ipilimumab. Now, researchers have reported data on PD-L1 expression and efficacy from a second interim analysis of KEYNOTE-006.

For the study, researchers enrolled 834 ipilimumab-naïve patients with advanced melanoma. Of the 821 evaluable patients for PD-L1 expression, 82% were PD-L1 positive. Participants were randomly assigned 1:1:1 to receive pembrolizumab 10 mg/kg every 2 weeks, every 3 weeks, or ipilimumab for 4 cycles.

Results showed that pembrolizumab, given every 2 or 3 weeks, significantly improved progression-free survival (P < .00001), overall survival (P = .0005 for every 2 weeks and P = .0036 for every 3 weeks), and objective response rate (P = .00003 and P = .0001, respectively) compared with ipilimumab.

Further, researchers found that among patients with PD-L1-positive tumors, patients who received pembrolizumab had improved progression-free survival (HR, 0.52; 95% CI, 0.43 – 0.64), overall survival (HR, 0.56; 95% CI, 0.43 – 0.74), and objective response rate (P < .00001) to a greater extent than patients with PD-L1-negative tumors (progression-free survival: HR, 0.83; 95% CI, 0.55 – 1.26; overall survival: HR, 0.94; 95% CI, 0.56 – 1.6; objective response rate: P < .00001).

Investigators also observed a correlation between degree of PD-L1 positivity and improved efficacy with pembrolizumab compared with ipilimumab.

These findings ultimately suggest that pembrolizumab monotherapy is appropriate in patients irrespective of PD-L1 status.

Reference

1. Carlino M, Ribas A, Gonzalez R, et al. KEYNOTE-006: PD-L1 expression and efficacy in patients (pts) treated with pembrolizumab (pembro) vs ipilimumab (IPI) for advanced melanoma. Oral presentation at: AACR Annual Meeting 2016; April 16-20, 2016; New Orleans, LA.