969P - Lenvatinib versus sorafenib as a second-line option in patients with unresectable hepatocellular carcinoma previously treated with atezolizumab plus bevacizumab: An observational study

Background

Atezolizumab plus bevacizumab (A+B) is a standard of care first-line (1L) systemic therapy for unresectable hepatocellular carcinoma (uHCC). However, optimal sequencing of systemic therapy post A+B remains unknown.

Methods

In this multicentre, retrospective study we examined efficacy and survival outcomes of patients (pts) with uHCC post A+B. Out of 935 pts treated with 1L A+B between May 2018 and August 2023, 454 discontinued 1L treatment and 214 started a second line (2L). Overall, 151 pts were treated with sorafenib (SOR) or lenvatinib (LEN) and were included in the analysis and assessment for overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR).

Results

Of 151 eligible pts, 78 (51.7%) pts were treated with SOR while 73 (48.3%) were treated with LEN. There were no significant differences in gender, ECOG performance status, viral status, best response to 1L, and pattern of progressions (intra- vs extra hepatic progression) between the two cohorts. Median age was slightly higher in the LEN cohort compared to the SOR one (67.3 years vs 63.7 years, p=0.023). In the overall 2L study population, LEN exposure was associated with longer median PFS (3.09 versus 2.03 months, p=0.005) and OS (12.5 versus 7.83, p=0.044) compared to SOR. In 107 response-evaluable patients, LEN was associated with better ORR (8.8% vs 0%) and DCR (50% vs 28.8%) compared to SOR (p=0.001). A neutrophil-to-lymphocyte ratio (NLR) >5 assessed prior second line initiation, was associated with worse OS in multivariate analysis (HR 2.2, CI 95% 1.07-4.67, p 0.033). When considering OS from the time of A+B initiation, the A+B-LEN sequence was associated with better OS than A+B-SOR (21.4 vs 14.73 months, p=0.017).

Conclusions

Within the limitations of a non-randomised observational study, the A+B-LEN sequence was associated with better efficacy than A+B-SOR, highlighting the need of further investigations to choose the right TKI therapy post immunotherapy discontinuation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

P. Lombardi: Financial Interests, Personal, Funding, ESMO Fellowship funded by BMS: ESMO. C. Celsa: Financial Interests, Personal, Speaker, Consultant, Advisor: Eisai, Ipsen, AstraZeneca, MSD; Financial Interests, Personal, Funding: Roche. T. Marron: Financial Interests, Personal, Advisory Board: Regeneron, AstraZeneca, Genentech, G1 Therapeutics, Arcus, Glenmark, Merck, NGM Bio, Glenmark, AbbVie, Fate; Financial Interests, Institutional, Coordinating PI: Regeneron, Genentech, Boehringer Ingelheim, Merck. A. Saeed: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Merck, Exelixis, Pfizer, Xilio Therapeutics, Taiho, Amgen, Autem Therapeutics, KAHR Medical, Daiichi Sankyo; Financial Interests, Institutional, Research Funding: AstraZeneca, Bristol Myers Squibb, Merck, Clovis, Exelixis, Actuate Therapeutics, Incyte Corporation, Daiichi Sankyo, Five Prime Therapeutics, Amgen, Innovent Biologics, Dragonfly Therapeutics, Oxford BioTherapeutics, Arcus Therapeutics, KAHR Medical; Financial Interests, Personal, Steering Committee Member, data safety monitoring board chair: Arcus Therapeutics. S. Ulahannan: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, IgM Biosciences; Financial Interests, Institutional, Research Funding: AbbVie, Inc., Adlai Notye, ArQule, Inc., AstraZeneca, Atreca, Boehringer Ingelheim, BMS, Celgene Corporation, Ciclomed LLC, Erasca, Evelo Biosciences, Inc., Exelixis, G1 Therapeutics, Inc., GSK, IGM biosciences, Incyte, Isofol, Klus Pharma, Inc., Macrogenics, Merck Co. Inc., Mersana Therapeutics, OncoMed Pharmaceuticals, Inc., Pfizer, Regeneron, Inc., Revolution Medicines, Inc., Synermore Biologics Co, Takeda, Tarveda Therapeutics, Tesaro, Tempest, Vigeo Therapeutics Inc. A. Dalbeni: Financial Interests, Institutional, Invited Speaker: AstraZeneca, Eisai; Financial Interests, Institutional, Advisory Board: Roche. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Lilly, Takeda, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Chugai, Eisai, AstraZeneca; Financial Interests, Institutional, Research Grant: Otsuka, Taiho, Eisai, AbbVie, GE Healthcare, Chugai. L. Rimassa: Financial Interests, Personal, Advisory Board, Consulting and advisory role: AbbVie, AstraZeneca, Basilea, Bayer, Elevar Therapeutics, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Jazz Pharmaceuticals, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology; Financial Interests, Personal, Invited Speaker, Lecture fees: AstraZeneca, Bayer, BMS, Guerbet, Incyte, Ipsen, Roche, Servier; Financial Interests, Personal, Other, Travel expenses: AstraZeneca; Financial Interests, Personal, Advisory Board: Zymeworks; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Exelixis, Incyte, Ipsen, Nerviano Medical Sciences, Roche, Servier; Financial Interests, Institutional, Coordinating PI, National (Italian) coordinating PI: AstraZeneca, BeiGene, Zymeworks; Financial Interests, Institutional, Local PI: Agios, Eisai, FibroGen, Lilly, MSD, Roche, Servier; Financial Interests, Institutional, Funding: Ipsen; Financial Interests, Institutional, Coordinating PI, European PI: AstraZeneca; Non-Financial Interests, Leadership Role, Treasurer: ILCA; Non-Financial Interests, Leadership Role, Chair: EORTC GITCG HPB/NET Task Force; Non-Financial Interests, Other, Special Expert Clinical Trials Europe: NCI HB Task Force. D.J. Pinato: Financial Interests, Personal, Speaker, Consultant, Advisor: Bayer Healthcare, AstraZeneca, Eisai, BMS, Roche, Ipsen, Mina Therapeutics, Boehringer Ingelheim, Ewopharma, H3B, DaVolterra, Mursla, Avammune Therapeutics, LifT Biosciences, Exact Sciences; Financial Interests, Personal, Other, Travel expenses: Bayer Healthcare, Roche, BMS; Financial Interests, Institutional, Research Grant: MSD, BMS, GSK. All other authors have declared no conflicts of interest.