ALBI score and outcomes in patients with hepatocellular carcinoma: post hoc analysis of the randomized controlled trial KEYNOTE-240

Abstract

Aims: This post hoc analysis evaluated albumin/bilirubin (ALBI) score, an objective measure of liver function, in patients receiving pembrolizumab plus best supportive care (BSC) compared with placebo plus BSC in the KEYNOTE-240 study.

Methods: Patients with confirmed hepatocellular carcinoma (HCC) and progression after/intolerance to sorafenib, Child-Pugh class A liver function, and Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned 2:1 to pembrolizumab 200 mg or placebo intravenously every 3 weeks plus BSC for ⩽35 cycles or until confirmed progression/unacceptable toxicity. Outcomes were assessed by ALBI grade.

Results: Of 413 patients, at baseline 116 had an ALBI grade 1 score (pembrolizumab, n = 74; placebo, n = 42) and 279 had an ALBI grade 2 score (n = 193; n = 86). Change from baseline in ALBI score to the end of treatment was similar in both arms [difference in least squares mean, -0.039; 95% confidence interval (CI): -0.169 to 0.091]. Time to ALBI grade increase was similar in both arms [median for pembrolizumab versus placebo: 7.8 versus 6.9 months; hazard ratio (HR) = 0.863 (95% CI: 0.625-1.192)]. Regardless of baseline ALBI grade, a trend toward improved overall survival was observed with pembrolizumab [grade 1: HR = 0.725 (95% CI: 0.454-1.158); grade 2: HR = 0.827 (95% CI: 0.612-1.119)].

Conclusion: Pembrolizumab did not adversely impact liver function compared with placebo in patients with HCC, as measured by changes in ALBI scores. A trend toward improved overall survival was observed with pembrolizumab in both ALBI grade groups. ClinicalTrials.gov identifier: NCT02702401.

Keywords: PD-1 inhibitor; albumin-bilirubin score; hepatocellular carcinoma; liver function; pembrolizumab.

Conflict of interest statement

Conflict of interest statement: A. Vogel has received fees from Roche, Eisai, Eli Lilly, Bristol Myers Squibb, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Bayer; P. Merle has participated in advisory boards for Bayer, Eisai, Eli Lilly, Roche, AstraZeneca, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and has received a grant from and participated in an advisory board for Ipsen; C. Verslype has received a grant for research, fees for speaking, and fees for serving as a consultant for Bayer, has received a grant for research and fees for serving as a consultant for Ipsen, and has received fees for serving as a consultant for Roche and Eli Lilly; R.S. Finn has received fees and a grant to his institution from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Bayer, Eli Lilly, Bristol Myers Squibb, Eisai, Pfizer, and Roche/Genentech, and fees from AstraZeneca and CStone; A.X. Zhu reports financial activities from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Eli Lilly, Bayer, Sanofi-Aventis, Eisai, Exelixis, and Roche as potential conflicts of interest; A-L Cheng has received fees for consulting from AstraZeneca, Bristol Myers Squibb, Eisai, Merck Serono, Novartis, Ono Pharmaceutical, Exelixis, Nucleix, Ipsen Innovation, Bayer Healthcare, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Roche/Genentech, BeiGene, CSR Pharma Group, F. Hoffmann-La Roche, and IQVIA, has received travel support from Roche/Genentech, IQVIA, and Bayer Yakuhin, and has received speaker fees from Eisai, Novartis, Ono Pharmaceutical, Bayer Yakuhin, and Amgen Taiwan; S.L. Chan, B-Y Ryoo, S. Qin have nothing to disclose; T. Yau reports a consulting or advisory role for Bristol Myers Squibb, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Exelixis, Ipsen, Eisai, AstraZeneca, Bayer, Novartis, EMD Serono, AbbVie, Pfizer, Eli Lilly, Sirtex, SillaJen, Taiho, OrigiMed, New B Innovation, and H3 Biomedicine, and has received honoraria from Bristol Myers Squibb, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Exelixis, Ipsen, Eisai, AstraZeneca, Bayer, Novartis, EMD Serono, AbbVie, Pfizer, Eli Lilly, Sirtex, SillaJen, Taiho, OrigiMed, New B Innovation, and H3 Biomedicine; J. Knox has received a grant for an investigator-initiated study from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and has received fees for consulting from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Ibsen, and Roche; B. Daniele has received fees from Ipsen, Eisai, Eli Lilly, AstraZeneca, Sanofi, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Bayer, Roche, and Amgen, and non-financial support from Ipsen, Sanofi, and Bayer; Z. Wei, Y. Miteva, U. Malhotra, and A.B. Siegel are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; M. Kudo has received a grant and fees from Eisai and EA Pharma, has received fees from Bayer, Bristol Myers Squibb, Eli Lilly, Ono Pharmaceutical, and Roche, and has received a grant from Gilead Sciences, Taiho, Sumitomo Dainippon Pharma, Takeda, Otsuka, and AbbVie.

© The Author(s), 2021.

Figures

Figure 1.

Kaplan–Meier estimates of time to ALBI grade increase.a,b aTime to ALBI grade increase was defined as the time from baseline ALBI measurement to the first postbaseline ALBI measurement that is ⩾1 grade higher than baseline ALBI grade. bData are reported for the as-treated population (n = 411). ALBI, albumin/bilirubin; BSC, best supportive care; CI, confidence interval; HR, hazard ratio; mo, months.

Figure 2.

Kaplan–Meier estimates of overall survival by (a) ALBI grade 1 and (b) ALBI grade 2.a aBased on BICR as per RECIST v1.1. ALBI, albumin/bilirubin; BICR, blinded independent central review; BSC, best supportive care; CI, confidence interval; HR, hazard ratio; mo, months; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1.

Figure 3.

Kaplan–Meier estimates of progression-free survival by (a) ALBI grade 1 and (b) ALBI grade 2.a aBased on BICR as per RECIST v1.1. ALBI, albumin/bilirubin; BICR, blinded independent central review; BSC, best supportive care; CI, confidence interval; HR, hazard ratio; mo, months; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1.

Figure 4.

Best percentage changes from baseline in size of target lesions by (a) ALBI grade 1 and (b) ALBI grade 2.a aBased on BICR per RECIST v1.1. ALBI, albumin/bilirubin; BICR, blinded independent central review; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1.