964P - Lenvatinib (L) and sorafenib (S) in patients (pts) with advanced or unresectable hepatocellular carcinoma (uHCC): An international, multicenter, phase IV study (STELLAR)

Background

L is a standard of care for pts with uHCC. This observational study characterized the hepatotoxicity/overall safety profile of first-line L in a real-world setting.

Methods

Study 508 is a prospective, nonrandomized, phase 4 study in Western pts (eg, Australia, Europe, and US) with uHCC treated with L or S via approved local prescribing practices. No formal statistical comparisons were conducted. The primary endpoint was to further characterize hepatotoxicity/overall safety with L. Medians for OS were estimated by the Kaplan-Meier method; 95% CIs were estimated via generalized Brookmeyer and Crowley method.

Results

As of Oct 31, 2022, 242 pts were treated (L, n=149; S, n=93; Table). Median study follow-up was 9.5 mos with L and 7.4 mos with S. Hepatotoxicity TEAEs were reported in 23% of pts treated with L (most commonly hepatic encephalopathy, 7%) and 33% of pts treated with S (most commonly ascites, 12%). Overall, TEAEs were reported in 80% of pts treated with L and 82% with S. Grade ≥ 3/serious TEAEs were reported in 40%/30% of pts treated with L, and 38%/31% treated with S. The most common TEAE was decreased appetite (25%) for L; and diarrhea (28%) for S. Fatal TEAEs (most due to unknown causes or attributable to underlying disease) were reported for 9% of pts with L (1 TEAE [hepatic encephalopathy] was treatment-related) and 4% of pts with S; frequency may have been impacted by pt age and poor ECOG PS with L. Median duration of treatment (DoT) was 4.8 mos with L and 4.4 mos with S. After adjusting for DoT, rates of fatal TEAEs were 0.2 with L and 0.1 with S. Median OS (95% CI) was 16.3 mos (11.8–NE) with L and 13.6 mos (8.4–NE) with S. Table: 964P

Conclusions

The incidence/severity of hepatoxicity/overall safety in this study were consistent with the known safety profile of first-line L in pts with uHCC. OS was consistent with results from the REFLECT study. Findings support the positive benefit-risk profile of L in first-line treatment of pts with uHCC.

Clinical trial identification

NCT04763408.

Editorial acknowledgement

Medical writing support was provided by Oxford PharmaGenesis Inc., Newtown, PA, USA.

Legal entity responsible for the study

Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

M. Peck Radosavljevic: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Eisai, Bristol Myers Squibb, MSD, AbbVie, Sobi, Shionogi; Financial Interests, Personal, Other, Honoraria; Travel, Accommodations, Expenses: Bayer, Roche, Gilead Sciences, Advanz Pharma, Ipsen; Financial Interests, Personal, Advisory Role: AstraZeneca, Bayer, Eisai, Bristol Myers Squibb, Roche, MSD, Gilead Sciences, AbbVie, Advanz Pharma, Ipsen, Sobi, Shionogi; Financial Interests, Institutional, Research Funding: Eisai, Bristol Myers Squibb, Roche, Ipsen, MSD, Gilead Sciences. Y. Ma: Financial Interests, Personal, Advisory Role: Roche, AstraZeneca/MedImmune, Faron Pharmaceuticals, Incyte; Financial Interests, Institutional, Research Funding: Eisai, AstraZeneca/Merck, Faron Pharmaceuticals, Mina Therapeutics. E. Mena: Financial Interests, Personal, Other, Honoraria: Gilead Sciences, Salix, Lilly, AbbVie; Financial Interests, Personal, Advisory Role: Galectin; Financial Interests, Personal, Speaker’s Bureau: Gilead, Salix, Lilly, AbbVie; Financial Interests, Institutional, Research Funding: Madrigal Pharmaceuticals, Gilead, Merck, Galectin, HighTide, Novo Nordisk, Altimmune, Akero, Salix, Cymabay Therapeutics. J.L. Lledó-Navarro: Financial Interests, Personal, Advisory Role: Eisai, MSD, Roche, AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche. J. Presa: Financial Interests, Personal, Advisory Role: Roche, Eisai, AstraZeneca, Gilead, AbbVie, Advanz Pharma, Orphalan; Financial Interests, Personal, Speaker’s Bureau: Roche, Eisai, AstraZeneca, Gilead, AbbVie, Advanz Pharma, Orphalan; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, Eisai, AstraZeneca, Gilead, AbbVie, Advanz Pharma; Financial Interests, Personal, Officer, Travel, Accommodations, Expenses: Orphalan. A. Weinmann: Financial Interests, Personal, Advisory Role: AstraZeneca, MSD, BMS GmbH & Co. KG, Servier; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, AbbVie. M.T. Levy: Financial Interests, Personal, Advisory Role: Gilead, AstraZeneca; Financial Interests, Personal, Research Funding: Gilead, AbbVie. A. Pellicelli: Financial Interests, Personal, Advisory Role: Eisai, MSD, Gilead; Financial Interests, Personal, Speaker’s Bureau: Eisai, Gilead. D.T. Waldschmidt: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Boehringer Ingelheim, Eisai, Bristol Myers Squibb, Incyte, Falk Foundation, MSD, Novartis, Roche Pharma AG, Servier, Ipsen; Financial Interests, Personal, Other, Travel: AstraZeneca, Ipsen, Roche Pharma AG, Servier. H.T. Sørensen: Financial Interests, Institutional, Other, Aarhus University has a contract with Eisai about consultancy but there is no personal relation: Eisai. L. Goyal: Financial Interests, Personal, Advisory Role: AbbVie, Alentis Therapeutics AG, AstraZeneca, Black Diamond, Cogent, Eisai, Exelixis, Genentech, H3Biomedicine, Kinnate, Incyte Corporation, Merck, Servier, Sirtex Medical Ltd., Surface Oncology, Taiho Oncology, Transthera Bio, Tyra Biosciences; Financial Interests, Personal, Other, DSMC: AstraZeneca. M. Ren, H. Saal, C.E. Okpara: Financial Interests, Personal, Full or part-time Employment: Eisai. T. Meyer: Financial Interests, Personal, Advisory Board: Ipsen, AstraZeneca, Eisai, Bayer, Roche, Adaptimmune, Boston Scientific, Signant Health; Financial Interests, Institutional, Research Grant: Bayer, BTG, MSD. All other authors have declared no conflicts of interest.