Abstract 937P
Background
The aim of this trial was to evaluate the efficacy and safety of lenvatinib (LEN) in combination with HAIC using cisplatin (CDDP) in patients (pts) with advanced hepatocellular carcinoma (HCC).
Methods
In this multicenter, open-labeled, single-arm, phase II trial, advanced HCC pts categorized as Child-Pugh class A with no prior history of systemic therapy were enrolled to receive Len+CDDP (lenvatinib: 12 mg once daily for patients weighing ≥60 kg, 8 mg once daily for patients weighing <60 kg; HAIC with CDDP: 65 mg/m2, day 1, every 4 to 6 weeks, up to a maximum of 6 cycles). The primary endpoint was the objective response rate (ORR) as assessed with modified RECIST by an independent review committee (IRC). The secondary endpoints were the ORR as assessed with RECIST v1.1 by IRC, the progression-free survival, the overall survival, and frequency of adverse events associated with the treatment. The threshold and expected ORRs were 20% and 40%, respectively at a one-sided significance level of 0.05, and statistical power of 80%. Based on these data, the number of pts required was estimated to be 35.
Results
A total of 36 pts were enrolled between September 2018 and March 2020, but two pts were judged as having no measurable lesions by the IRC. Among the remaining 34 evaluable pts, the ORR by the IRC according to modified RECIST and RECISTv1.1 were 64.7% (95% confidence interval (CI): 46.5%-80.3%), and 45.7% (95% CI: 28.8%-63.4%), respectively. The study treatment was discontinued in all the 36 pts for the following reasons: disease progression (24 pts, 67%), adverse events (9 pts, 25%), others (3 pts, 8%). The median progression-free survival and overall survival were 6.3 months (95% CI: 5.1-7.9 months) and 17.2 months (95% CI: 10.9-NA, months), respectively. The main grade 3-4 adverse events were increased AST (34%), hyponatremia (25%), leukopenia (22%), increased ALT (19%), and hypertension (11%). There were no treatment-related deaths in this series.
Conclusions
Len+CDDP yielded very favorable ORR and overall survival, and was well-tolerated in pts with advanced HCC. Further evaluation of this regimen in a phase III trial is warranted.
Clinical trial identification
jRCTs031180019.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Eisai Co., Ltd. Japan.
Disclosure
M. Ikeda: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Chugai; Financial Interests, Personal, Advisory Board: Eli Lilly Japan; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Nihon Servier; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Ono; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Eli Lilly Japan; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Nihon Servier; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Otsuka; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Yakult; Financial Interests, Personal, Invited Speaker: Teijin Pharma; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Institutional, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Institutional, Invited Speaker: Eisai; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Eli Lilly Japan; Financial Interests, Institutional, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Institutional, Invited Speaker: Merck Serono; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Ono; Financial Interests, Institutional, Invited Speaker: Yakult; Financial Interests, Institutional, Invited Speaker: ASLAN; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Takeda; Financial Interests, Institutional, Invited Speaker: J-Pharma; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Chiome Bioscience; Financial Interests, Institutional, Invited Speaker: GlaxoSmithKline; Financial Interests, Institutional, Invited Speaker: Nihon Servier; Financial Interests, Institutional, Invited Speaker: Delta-Fly Pharma; Financial Interests, Personal, Invited Speaker: ASLAN; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Nihon Servier; Financial Interests, Personal, Invited Speaker: Takeda. T. Yamashita: Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Lilly. S. Ogasawara: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Eli Lilly. M. Kudo: Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Eli Lily; Non-Financial Interests, Institutional, Research Grant: AbbVie; Non-Financial Interests, Institutional, Research Grant: Chugai; Non-Financial Interests, Institutional, Research Grant: EA Pharma; Non-Financial Interests, Institutional, Research Grant: Eisai; Non-Financial Interests, Institutional, Research Grant: Gilead Sciences; Non-Financial Interests, Institutional, Research Grant: Otsuka; Non-Financial Interests, Institutional, Research Grant: Sumitomo Dainippon; Non-Financial Interests, Institutional, Research Grant: Taiho; Non-Financial Interests, Institutional, Research Grant: Takeda. Y. Inaba: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Principal Investigator: AstraZenaca; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: Takeda; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical. M. Morimoto: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Eli Lilly. K. Tsuchiya: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co; Financial Interests, Personal, Invited Speaker: Eli Lilly Japan. S. Shimizu: Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Yakult; Financial Interests, Institutional, Research Grant: Incyte Corporation; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Delta-Fly Pharma. Y. Kojima: Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Yakult; Financial Interests, Institutional, Research Grant: Beigene; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Ono; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Eisai. A. Hiraoka: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Otsuka Pharmaceutical; Financial Interests, Personal, Invited Speaker: Eli Lilly. H. Aikata: Financial Interests, Personal, Invited Speaker: Eisai. T. Okusaka: Financial Interests, Personal, Advisory Board: Taiho Pharmaceutical; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Dainippon Sumitomo Pharma; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Nihon Servier; Financial Interests, Personal, Advisory Board: Eli lilly; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Meiji Seika Pharma; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Takara Bio; Financial Interests, Personal, Advisory Board: Nippon Shinyaku; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Mundipharma; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Yakut Honsha; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal, Invited Speaker: Chugai Pharma; Financial Interests, Personal, Invited Speaker: Teijin Pharma; Financial Interests, Personal, Invited Speaker: Eli lilly; Financial Interests, Personal, Invited Speaker: Nihon Servier; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Chugai Pharma; Financial Interests, Institutional, Principal Investigator: Eisai; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Institutional, Principal Investigator: Bristol-Myers Squibb; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: Baxter; Financial Interests, Institutional, Principal Investigator: Taiho Pharmaceutical; Financial Interests, Institutional, Principal Investigator: Dainippon Sumitomo Pharma; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: AstraZeneca. J. Furuse: Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Merck Bio; Financial Interests, Institutional, Research Grant: J-Pharma; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Chugai Pharma; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Yakult Honsha; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Mochida; Financial Interests, Institutional, Research Grant: Sanofy; Financial Interests, Institutional, Research Grant: Sumitomo Dainippon; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Incyte Japan; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Eli Lilly Japan; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Yakult Honsha; Financial Interests, Personal, Invited Speaker: Chugai Pharma; Financial Interests, Personal, Invited Speaker: Novartis Pharma; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Mylan EPD; Financial Interests, Personal, Invited Speaker: EA Pharma; Financial Interests, Personal, Invited Speaker: Kyowa Hakko Kirin; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Teijin pharma; Financial Interests, Personal, Invited Speaker: Servier Japan; Financial Interests, Personal, Invited Speaker: Incyte Japan; Financial Interests, Personal, Invited Speaker: Eisai. All other authors have declared no conflicts of interest.