Evolution of Survival Impact of Molecular Target Agents in Patients with Advanced Hepatocellular Carcinoma.

Background and Aims: The prognosis of patients with advanced hepatocellular carcinoma (HCC) is expected to improve as multiple molecular target agents (MTAs) are now available. However, the impact of the availability of sequential MTAs has not been fully verified yet.
Approach and Results: We retrospectively collected the data on the whole clinical course of 877 patients who received any MTAs as first-line systemic therapy for advanced HCC between June 2009 and March 2019. The study population was divided into 3 groups according to the date of first-line MTA administration (period 1: 2009-2012, n = 267; period 2: 2013-2016, n = 352; period 3: 2017-2019, n = 258). Then, we compared the number of MTAs used, overall survival (OS), and MTA treatment duration among the 3 groups. Analysis was also performed separately for advanced-stage and nonadvanced-stage HCC. The proportion of patients who received multiple MTAs was remarkably increased over time (1.1%, 10.2%, and 42.6% in periods 1, 2, and 3, respectively, p < 0.001). The median OS times were prolonged to 10.4, 11.3, and 15.2 months in periods 1, 2, and 3, respectively ( p = 0.016). Similarly, the MTA treatment durations were extended (2.7, 3.2, and 6.6 months in periods 1, 2, and 3, respectively; p < 0.001). We confirmed that the correlation between OS and MTA treatment duration was strengthened (period 1: 0.395, period 2: 0.505, and period 3: 0.667). All these trends were pronounced in the patients with advanced-stage HCC but limited in the patients with nonadvanced-stage HCC.
Conclusions: The availability of multiple MTAs had steadily improved the prognosis of patients with advanced HCC patients, particularly advanced-stage HCC patients.
Competing Interests: Sadahisa Ogasawara received honoraria from Bayer, Leverkusen, Germany; Eisai, Tokyo, Japan; Eli Lilly, Indianapolis, IN, USA; Chugai Pharma, Tokyo, Japan; AstraZeneca, Cambridge, UK; and Merck & Co., Inc., Kenilworth, NJ, USA, consulting or advisory fees from Bayer, Eisai, Merck & Co., Inc., Chugai Pharma, Eli Lilly, and AstraZeneca, and research grants from Bayer, AstraZeneca, and Eisai. Michihisa Moriguchi received honoraria from Eisai, Bayer, Eli Lilly, and Chugai Pharma, and consulting or advisory fees from Eisai, Bayer, Eli Lilly, and Chugai Pharma. Naoki Morimoto received research grants from Eisai and Abbvie, Lake Bluff, IL, USA. Yoshihiko Ooka received honoraria from Eisai. Tatsuo Kanda received research grants from Towa Pharmaceutical, Osaka, Japan; Abbvie, Chugai Pharma, Daiichi Sankyo, Tokyo, Japan; and Shionogi, Osaka, Japan. Kengo Nagashima received a lecture fee from Pfizer, New York, NY, USA. Norio Isoda received research grants from Eisai and Abbvie. Takeshi Aramaki received speaker's bureau from Eli Lilly, Chugai Pharma, Termo, Milano, Italy; Eisai, and Taiho Pharma, Tokyo, Japan. Yoshito Itoh received speaker's bureau from MSD, Kenilworth, NJ, USA, Eisai, and Chugai Pharma; and research grants from MSD, Eisai, Bayer, and Chugai Pharma. Naoya Kato received honoraria from Bayer, Eisai, Sumitomo Dainippon Pharma, Tokyo, Japan, and Merck & Co., Inc.; consulting or advisory fees from Bayer and Eisai; and research grants from Bayer and Eisai. The other authors have no conflicts of interest to declare.
(Copyright © 2021 by S. Karger AG, Basel.)