KEYNOTE-006 study of pembrolizumab (pembro) versus ipilimumab (ipi) for advanced melanoma: Efficacy by PD-L1 expression and line of therapy.

9513 Background: In KEYNOTE-006 (NCT01866319), pembro (MK-3475) provided superior OS and PFS and a lower grade 3-5 treatment-related AE rate over ipi in patients (pts) with advanced melanoma and ≤ 1 prior therapy. We assessed the impact of PD-L1 expression and prior therapy on outcomes in KEYNOTE-006. Methods: Pts were randomized to pembro 10 mg/kg Q2W or Q3W or ipi 3 mg/kg Q3W. Pembro was given for 24 mo or until progression, intolerable toxicity, or investigator decision. Ipi was given for 4 cycles or until progression, intolerable toxicity, or investigator decision. PD-L1 was assessed by IHC using the 22C3 antibody; positivity was defined as ≥ 1% staining in tumor and adjacent immune cells. Response was assessed at wk 12, Q6W until wk 48, then Q12W. Survival follow-up was every 12 wk. Primary end points were OS and PFS (RECIST v1.1, central review). Data cutoff date was Mar 3, 2015. Pembro arms were pooled for this analysis. Results: Of the 834 pts enrolled, 80% were PD-L1+, 18% were PD-L1–, and 2% were PD-L1 unknown; 66% were treatment naive and 34% had 1 line of prior therapy. PFS and ORR were improved with pembro regardless of line of therapy or PD-L1 status (Table); OS was improved with pembro in all but PD-L1– pts, although the sample size was small and the CI was wide. For pembro, the best outcomes occurred in treatment-naive pts and those with PD-L1+tumors, with marginal additional benefit in pts with both characteristics (Table). There was a relationship between increasing PD-L1 expression and improved outcomes with pembro vs ipi when PD-L1 was scored as IHC 0 (0% staining), 1 ( < 1%), 2 (1-9%), 3 (10-32%), 4 (33-65%), and 5 ( ≥ 66%). Conclusions: Pembro provides benefit over ipi in pts with advanced melanoma, regardless of tumor PD-L1 expression or whether pts received prior therapy. Clinical trial information: NCT01866319.Pembro vs Ipi PD-L1+ PD-L1– Treatment Naive 1 Prior Therapy PD-L1+, Treatment Naive PFS 6-mo rate, % 51 vs 25 32 vs 28 52 vs 28 38 vs 23 55 vs 28 HR (95% CI) 0.52 (0.43-0.64) 0.83 (0.55-1.26) 0.55 (0.44-0.69) 0.74 (0.55-0.99) 0.49 (0.38-0.63) OS 6-mo rate, % 87 vs 74 81 vs 73 87 vs 76 83 vs 71 88 vs 75 HR (95% CI) 0.56 (0.43-0.73) 0.95 (0.56-1.62) 0.63 (0.46-0.85) 0.67 (0.45-0.98) 0.55 (0.39-0.78) ORR, % 39 vs 13 25 vs 13 40 vs 13 29 vs 12 43 vs 13

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