Abstract CT004: KEYNOTE-006: PD-L1 expression and efficacy in patients (Pts) treated with pembrolizumab (pembro) vs ipilimumab (IPI) for advanced melanoma
Authors: Matteo Carlino, Antoni Ribas, Rene Gonzalez, Christoph Hoeller, Gil Bar-Sela, Catherine Barrow, David Chao, Pascal Wolter, Carola Berking, Oddbjørn Straume, Alfonso Berrocal, Esther Holgado, Tara C. Gangadhar, Geoffrey Weiss, Honghong Zhou, Kenneth Emancipator, Nageatte Ibrahim, Dirk Schadendorf
Journal: Cancer Research (2016)

Abstract Background: The anti-PD-1 antibody pembro and the anti-CTLA-4 antibody IPI have shown efficacy in advanced melanoma. In KEYNOTE-006 (NCT01866319), pembro significantly improved PFS, ORR, and OS compared with IPI. Here, we present data on PD-L1 expression and efficacy at the second interim analysis. Methods: IPI-naive pts were randomly assigned in a 1:1:1 ratio to pembro 10 mg/kg Q2W or Q3W or 4 cycles of IPI. Randomization was stratified by PD-L1 expression using Dako's PD-L1 IHC 22C3 pharmDx assay (positive [membranous PD-L1 staining in ?1% of tumor and adjacent immune cells] vs negative), ECOG PS (0 vs 1), and line of therapy (1st vs 2nd). IHC scores of 0 (0% staining), 1 (&amp;lt;1%), 2 (1%-9%), 3 (10%-32%), 4 (33%-65%), and 5 (?66%) were used to score PD-L1 expression. Response was assessed per central RECIST v1.1. Efficacy end points, PFS, OS, and ORR, were compared based on PD-L1 status and IHC score. Data cutoff date was March 3, 2015. Results: Overall, 834 pts enrolled. Of the 821 PD-L1 evaluable pts, 671 (82%) were PD-L1 positive. Pembro significantly improved PFS (P &amp;lt; .00001 for both arms), OS (P = .0005 for Q2W and P = .0036 for Q3W), and ORR (P = .00003 for Q2W and P = .00001 for Q3W) compared with IPI. Improved efficacy in pts with PD-L1-positive (PFS: HR = 0.52; 95% CI, 0.43-0.64; OS: HR = 0.56; 95% CI, 0.43-0.74; ORR: P &amp;lt; .00001) vs PD-L1-negative tumors (PFS: HR = 0.83; 95% CI, 0.55-1.26; OS: HR = 0.94; 95% CI, 0.56-1.6; ORR: P &amp;lt; .00001) was observed in combined pembro arms compared with IPI. There was a correlation between degree of PD-L1 positivity and improved PFS, OS, and ORR in pembro compared with IPI (Table). Efficacy between the 2 pembro arms was comparable. Conclusions: PD-L1 positivity is associated with improved efficacy with pembro compared with IPI. Higher degree of PD-L1 positivity correlated with greater improvement in PFS, OS, and ORR. As evidenced by treatment effect in all groups, pembro monotherapy is appropriate in pts regardless of PD-L1 status. Citation Format: Matteo Carlino, Antoni Ribas, Rene Gonzalez, Christoph Hoeller, Gil Bar-Sela, Catherine Barrow, David Chao, Pascal Wolter, Carola Berking, Oddbjørn Straume, Alfonso Berrocal, Esther Holgado, Tara C. Gangadhar, Geoffrey Weiss, Honghong Zhou, Kenneth Emancipator, Nageatte Ibrahim, Dirk Schadendorf. KEYNOTE-006: PD-L1 expression and efficacy in patients (Pts) treated with pembrolizumab (pembro) vs ipilimumab (IPI) for advanced melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT004.