PMID- 37325487
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230619
IS  - 2235-1795 (Print)
IS  - 1664-5553 (Electronic)
IS  - 1664-5553 (Linking)
VI  - 12
IP  - 2
DP  - 2023 Jun
TI  - Regorafenib versus Cabozantinib as a Second-Line Treatment for Advanced 
      Hepatocellular Carcinoma: An Anchored Matching-Adjusted Indirect Comparison of 
      Efficacy and Safety.
PG  - 145-155
LID - 10.1159/000527403 [doi]
AB  - INTRODUCTION: The tyrosine kinase inhibitors regorafenib and cabozantinib remain 
      the mainstay in second-line treatment of advanced hepatocellular carcinoma (HCC). 
      There is currently no clear evidence of superiority in efficacy or safety to 
      guide choice between the two treatments. METHODS: We conducted an anchored 
      matching-adjusted indirect comparison using individual patient data from the 
      RESORCE trial of regorafenib and published aggregate data from the CELESTIAL 
      trial of cabozantinib. Second-line HCC patients with prior sorafenib exposure of 
      >/=3 months were included in the analyses. Hazard ratios (HRs) and restricted mean 
      survival time (RMST) were estimated to quantify differences in overall survival 
      (OS) and progression-free survival (PFS). Safety outcomes compared were rates of 
      grade 3 or 4 adverse events (AEs), occurring in >10% of patients, and 
      discontinuation or dose reduction due to treatment-related AEs. RESULTS: After 
      matching adjustment for differences in baseline patient characteristics, 
      regorafenib showed a favorable OS (HR, 0.80; 95% CI: 0.54, 1.20) and 
       approximately 3-month-longer RMST over cabozantinib (RMST difference, 2.76 months; 95% CI: 
      -1.03, 6.54), although not statistically significant. For PFS, there was no 
      numerical difference in HR (HR, 1.00; 95% CI: 0.68, 1.49) and no clinically 
      meaningful difference based on RMST analyses (RMST difference, -0.59 months; 95% 
      CI: -1.83, 0.65). Regorafenib showed a significantly lower incidence of 
      discontinuation (risk difference, -9.2%; 95% CI: -17.7%, -0.6%) and dose 
      reductions (-15.2%; 95% CI: -29.0%, -1.5%) due to treatment-related AEs (any 
      grade). Regorafenib was also associated with a lower incidence (not statistically 
      significant) of grade 3 or 4 diarrhea (risk difference, -7.1%; 95% CI: -14.7%, 
      0.4%) and fatigue (-6.3%; 95% CI: -14.6%, 2.0%). CONCLUSION: This indirect 
      treatment comparison suggests, relative to cabozantinib, that regorafenib could 
      be associated with favorable OS (not statistically significant), lower rates of 
      dose reductions and discontinuation due to treatment-related AEs, and lower rates 
      of severe diarrhea and fatigue.
CI  - Copyright (c) 2022 by The Author(s). Published by S. Karger AG, Basel.
FAU - Merle, Philippe
AU  - Merle P
AD  - Hepatology and Gastroenterology Unit, Croix-Rousse Hospital, Hospices Civils de 
      Lyon, Lyon, France, INSERM U1052, Centre de Recherche en Cancerologie de Lyon, 
      Lyon, France.
FAU - Kudo, Masatoshi
AU  - Kudo M
AD  - Department of Gastroenterology and Hepatology, Kindai University Faculty of 
      Medicine, Osaka, Japan.
FAU - Krotneva, Stanimira
AU  - Krotneva S
AD  - Evidera, Montreal, Quebec, Canada.
FAU - Ozgurdal, Kirhan
AU  - Ozgurdal K
AD  - Bayer Consumer Care AG, Basel, Switzerland.
FAU - Su, Yun
AU  - Su Y
AD  - Bayer HealthCare Pharmaceuticals, Inc., Whippany, New Jersey, USA.
FAU - Proskorovsky, Irina
AU  - Proskorovsky I
AD  - Evidera, Montreal, Quebec, Canada.
LA  - eng
PT  - Journal Article
DEP - 20221007
PL  - Switzerland
TA  - Liver Cancer
JT  - Liver cancer
JID - 101597993
PMC - PMC10267565
OTO - NOTNLM
OT  - Cabozantinib
OT  - Decision-making
OT  - Hepatocellular carcinoma
OT  - Indirect treatment comparison
OT  - Regorafenib
OT  - Tyrosine kinase inhibitor
COIS- Philippe Merle has received consulting fees from Bayer, Ipsen, Eli Lilly, Eisai, 
      Roche, AstraZeneca, Bristol-Myers Squibb, and Roche; travel expenses from Bayer, 
      Ipsen, Roche, and Bristol-Myers Squibb; and research funding (to institution) 
      from Ipsen. Masatoshi Kudo has received grants from Chugai, Otsuka, Takeda, 
      Taiho, Sumitomo Dainippon, Daiichi Sankyo, MSD, Eisai, Bayer, EA Pharma, Ono 
      Pharma, Gilead Sciences, and AbbVie; lecturing fees from Bayer, Eisai, MSD, BMS, 
      EA Pharma, Eli Lilly, Chugai, and Ajinomoto; advisory and consultancy fees from 
      Bayer, Eisai, Ono, Kowa, MSD, BMS, Roche, Chugai, and Taiho. Masatoshi Kudo is 
      Editor-in-Chief of Liver Cancer. Stanimira Krotneva and Irina Proskorovsky are 
      employed by Evidera. Kirhan Ozgurdal and Yun Su are employed by Bayer.
EDAT- 2023/06/16 06:42
MHDA- 2023/06/16 06:43
PMCR- 2022/10/07
CRDT- 2023/06/16 04:25
PHST- 2022/04/04 00:00 [received]
PHST- 2022/09/07 00:00 [accepted]
PHST- 2023/06/16 06:43 [medline]
PHST- 2023/06/16 06:42 [pubmed]
PHST- 2023/06/16 04:25 [entrez]
PHST- 2022/10/07 00:00 [pmc-release]
AID - lic-0012-0145 [pii]
AID - 10.1159/000527403 [doi]
PST - epublish
SO  - Liver Cancer. 2022 Oct 7;12(2):145-155. doi: 10.1159/000527403. eCollection 2023 
      Jun.