Updated efficacy and safety of KEYNOTE-224: A phase II study of pembrolizumab (pembro) in patients with advanced hepatocellular carcinoma (HCC).
Masatoshi Kudo, Richard S. Finn, Julien Edeline, Stéphane Cattan, Sadahisa Ogasawara, Daniel H. Palmer, Chris Verslype, Vittorina Zagonel, Lætitia Fartoux, Arndt Vogel, Debashis Sarker, Gontran Verset, Stephen L. Chan, Jennifer J. Knox, Bruno Daniele, Ellen B. Gurary, Abby B. Siegel, Lokesh Jain, Ann‐Lii Cheng, Andrew X. Zhu, for the KEYNOTE-224 Investigators
Abstract
518 Background: Pembro received accelerated approval in pts with advanced HCC in the second-line setting based on results of the KEYNOTE-224 trial. Results of a 2 y follow-up analysis of the efficacy and safety in this trial are presented here. Methods: Eligible pts had histologically confirmed HCC, radiographic progression on/intolerance to sorafenib and disease not amenable to curative treatment, Child Pugh A, ECOG PS 0-1 and BCLC stage C or B. Pts received pembro 200 mg IV Q3W for 2 y or until disease progression, unacceptable toxicity, consent withdrawal or investigator decision. Response was assessed every 9 wk. Primary endpoint was ORR (RECIST v1.1, central review). Secondary endpoints were DOR, DCR, PFS, OS and safety. Results: Efficacy and safety were assessed in 104 pts. The median time from randomization to data cutoff (Jun 05, 2019) was 31.2 mo (27.5-35.5 mo). Pt characteristics were: median age 68 y (43-87), 21.2% HBV+, 25% HCV+, 94.2% Child Pugh A, 79.8% had PD on sorafenib, 17.3% had MVI and 64.4% had extrahepatic disease. ORR was 18.3% (95% CI 11.4-27.1) and was similar across subgroups. Median DOR was 21.0 mo (3.1-28+ mo); 77% had responses lasting ≥12 mo (Kaplan Meier). Best overall responses were 4 (3.8%) CRs, 15 (14.4%) PRs, 45 (43.3%) SDs and 34 (32.7%) PDs; DCR was 61.5%. The median PFS (95% CI) was 4.9 mo (3.5-6.7) and OS was 13.2 mo (9.7-15.3). PFS 24 mo rate was 11.3% and OS 24 mo rate was 30.8%. ORR was shown to be a predictor of longer OS by landmark analysis. Treatment-related AEs occurred in 76 (73.1%) pts; the most common AEs were fatigue, increased aspartate aminotransferase, pruritus and diarrhea observed in ≥10% pts. Grade ≥3 treatment related AEs occurred in 27 (26.0%) pts. Immune-mediated hepatitis occurred in 3 (2.9%) pts; no cases of HBV/HCV flare were identified. Conclusions: At 2 y follow-up, pembro continued to provide durable anti-tumor activity and prolonged survival (30.8% OS, 24 mo rate), further supporting its use in previously treated pts with advanced HCC. With longer follow-up, increases in ORR (18.3% vs 17.0%), DOR ≥12 mo (77.0% vs 61.4%) and CR rates (3.8% vs 1%) were seen. The safety profile was similar to the primary analysis. Clinical trial information: NCT02702414.