Vanderbilt University Medical Center, Nashville, TN
Igor Puzanov , Reinhard Dummer , Jacob Schachter , Anna C. Pavlick , Rene Gonzalez , Paolo Antonio Ascierto , Kim Allyson Margolin , Omid Hamid , Sanjiv S. Agarwala , Matteo S. Carlino , Jochen Utikal , Michal Lotem , Antoni Ribas , Peter Mohr , Charlotte M. Roach , Marisa Dolled-Filhart , Xiaoyun Nicole Li , Scot Ebbinghaus , Soonmo Peter Kang , Adil Daud
Background: Pembro is an anti–PD-1 antibody approved for treating advanced MEL that progressed following IPI and, if BRAFV600 mutant, a BRAF inhibitor. In KEYNOTE-002 (NCT01704287), pembro doses of 2 mg/kg and 10 mg/kg every 3 wk (Q3W) significantly improved PFS compared with investigator-choice chemotherapy in IPI-R MEL (P < .0001), with no difference between pembro doses (P = .44). Data from KEYNOTE-001 showed that PD-L1 positivity was correlated with a higher ORR and longer PFS in MEL pts. We evaluated efficacy in PD-L1+ and PD-L1– MEL pts enrolled in KEYNOTE-002. Methods: 540 pts with advanced IPI-R MEL were randomized 1:1:1 to pembro 2 or 10 mg/kg every 3 wk (Q3W) or chemotherapy. PD-L1 expression was assessed centrally by IHC using the 22C3 antibody. The cut point for positivity was staining in ≥1% of tumor cells. Response was assessed at wk 12 and every 6 wk thereafter (RECIST v1.1, central review). Primary end points were PFS and OS (final analysis planned after 370 deaths occur). ORR and the relationship between PD-L1 expression and efficacy were secondary end points. Data for the pembro arms were pooled. Results: 421/540 pts enrolled (78%) had tumors evaluable for PD-L1 expression; 291 (69%) were PD-L1+, 130 (31%) were PD-L1–. Pembro prolonged PFS and increased ORR compared with control in PD-L1+ and PD-L1– pts (Table). Among pembro-treated pts, ORR was higher in PD-L1+ pts, but the CIs were overlapping, and there was no difference in duration of response (DOR) based on PD-L1 expression. There was no prognostic effect in the control arm. Conclusions: Pembro improved efficacy over chemotherapy in both PD-L1+ and PD-L1– IPI-R advanced MEL. These data indicate that in IPI-R MEL pts, pembro therapy should not be limited to pts with PD-L1+ tumors. Clinical trial information: NCT01704287
Total | PD-L1+ | PD-L1– | ||||
---|---|---|---|---|---|---|
Pembro n = 361 | Control n = 179 | Pembro n = 193 | Control n = 98 | Pembro n = 93 | Control n = 37 | |
PFS, HRa (95% CI) | 0.53 (0.43–0.65) | 0.52 (0.39–0.68) | 0.60 (0.38–0.94) | |||
6-mo PFS, % | 36 | 16 | 40 | 13 | 26 | 22 |
ORR, % (95% CI) | 23 (19–28) | 4 (2–9) | 26 (20–33) | 4 (1–10) | 15 (8–24) | 8 (2–22) |
DOR, wk, median (range) | NR (5+ – 50+) | 37 ( 7+ – 41) | NR (5+ – 50+) | 41 (18 + – 41) | NR (6+ – 48+) | 37 (7+ – 37) |
aPembro vs control.
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