Abstract 1003P
Background
Albumin/bilirubin (ALBI) score measures liver function in HCC using objective laboratory variables. KEYNOTE-240 (NCT02702401) was a phase III study in pts with previously treated, advanced HCC that demonstrated reduced risk of death with pembrolizumab (pembro) vs placebo (pbo), but prespecified significance criteria were not met. We hypothesized that deterioration of liver function, as measured by change in ALBI score, would not be adversely affected by pembro vs pbo.
Methods
Eligible pts had confirmed HCC, progression on/intolerance to sorafenib, Child-Pugh A disease, and ECOG performance status 0-1. Pts were randomized 2:1 to pembro 200 mg or pbo IV every 3 wk + best supportive care for ≤35 cycles or until confirmed progression/unacceptable toxicity. This post hoc analysis assessed change from BL in ALBI score and time to increase in ALBI grade in both arms. Efficacy was assessed in ALBI grade 1 and 2 subgroups. Data cutoff: 2 Jan 2019.
Results
Of 413 pts, 116 had BL ALBI grade 1 (pembro, n=74; pbo, n=42) and 279 had BL ALBI grade 2 (pembro, n=193; pbo, n=86). Change from BL in ALBI score to the end of treatment was similar in both arms (difference in least-squares mean –0.037; 95% CI –0.167, 0.093). Time to ALBI grade increase was similar in both arms (median 7.8 mo on pembro vs 6.9 mo on pbo; hazard ratio [HR] 0.863 [95% CI 0.625, 1.192]) (Table). Regardless of BL ALBI grade, pembro improved overall survival (OS; grade 1: HR 0.725 [95% CI 0.454, 1.158]; grade 2: HR 0.827 [95% CI 0.612, 1.119]).
Conclusions
Liver function in pts with HCC as measured by change in ALBI score from BL was not adversely affected by pembro vs pbo. Time to ALBI grade increase was similar in both arms. OS benefit with pembro was observed in both ALBI grade groups. Table: 1003P
Analysis of Time to ALBI Grade Increase
| Treatment | N | Events, n (%) | Median,a months (95%CI) | HR (95% CI)b | P Valuec |
| Pembro | 278 | 118 (42.4) | 7.8 (6.4, 14.3) | 0.863 (0.625, 1.192) | 0.1828 |
| Pbo | 133 | 56 (42.1) | 6.9 (4.9, 12.7) |
aFrom product-limit (Kaplan-Meier) method for censored data.bBased on stratified Cox regression model with treatment as a covariate.cOne-sided P value based on stratified log-rank test.
Clinical trial identification
NCT02702401, March 8, 2016.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA) and funded by Merck Sharp & Dohme Corp.
Legal entity responsible for the study
Merck Sharp & Dohme Corp.
Funding
Merck Sharp & Dohme Corp.
Disclosure
A. Vogel: Advisory/Consultancy: Novartis, Lilly, Roche, Amgen, Bayer, Baxalta, AstraZeneca, Eisai, BTG, Ipsen, Pierre Fabre; Travel/Accommodation/Expenses: Bayer, Roche, Ipsen; Honoraria (self): Novartis, Sanofi, Amgen, Delcath Systems, Lilly, Bristol-Myers Squibb, MSD, Pierre Fabre, Ipsen, Janssen; Research grant/Funding (self): Novartis. P. Merle: Advisory/Consultancy: Bayer Schering Pharma; Honoraria (self): Bayer Schering Pharma, Ipsen, EISAI, Bristol-Myers Squibb, Merck, Lilly, AstraZeneca, Roche. C. Verslype: Advisory/Consultancy: Novartis, Bayer, Ipsen; Speaker Bureau/Expert testimony: Bayer; Travel/Accommodation/Expenses: Ipsen, Bayer; Research grant/Funding (institution): Bayer. R.S. Finn: Advisory/Consultancy: Pfizer, Bayer, Novartis, Bristol-Myers Squibb, Merck, Eisai, Lilly, Genentech/Roche, AstraZeneca, Exelixis, C Stone Pharma; Speaker Bureau/Expert testimony: Novartis; Research grant/Funding (institution): Pfizer, Bayer, Novartis, Eisai, Lilly, Merck, Bristol-Myers Squibb, Roche/Genentech. A.X. Zhu: Advisory/Consultancy: Eisai, Merck, AstraZeneca, Bayer, Exelixis, Lilly, Roche/Genentech; Research grant/Funding (institution): Lilly, Bayer, Bristol-Myers Squibb, Novartis, Merck. A-L. Cheng: Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Eisai, Merck Serono, Novartis, Ono Pharmaceutical, Exelixis, Nucleix, Ipsen Innovation, Bayer Healthcare, Merck Sharp Dohme, Roche/Genentech, BeiGene, CSR Pharma Group, F. Hoffmann-La Roche, IQVIA; Advisory/Consultancy: AstraZeneca, Bristol-Myers Squibb, Eisai, Merck Serono, Novartis, Ono Pharmaceutical, Exelixis, Nucleix, IPSEN Innovation, Bayer Healthcare, Merck Sharp Dohme, Roche/Genentech, BeiGene, CSR Pharma Group, F. Hoffmann-La Roche, IQVIA; Travel/Accommodation/Expenses: Bayer Yakuhin, Roche/Genentech, IQVIA; Speaker Bureau/Expert testimony: ayer Yakuhin, Novartis, Eisai, Ono Pharmaceutical, Amgen Taiwan. S.L. Chan: Advisory/Consultancy: Novartis, MSD Oncology, AstraZeneca/MedImmune. T. Yau: Advisory/Consultancy: Bristol-Myers Squibb, MSD Oncology. Z. Wei: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck. U. Malhotra: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck. A.B. Siegel: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck. M. Kudo: Advisory/Consultancy: MSD, Eisai, Ono Pharmaceutical, Bristol-Myers Squibb; Honoraria (self): MSD, Eisai, Bayer; Research grant/Funding (institution): Otsuka, Taiho Pharmaceutical, AbbVie, Takeda, Eisai, Gilead Sciences, EA Pharma. All other authors have declared no conflicts of interest.