Kelley R.K.Mollon P.Blanc J.-F.Daniele B.Yau T.ANN-LII CHENGValcheva V.Marteau F.Guerra I.Abou-Alfa G.K.2021-08-312021-08-3120200741-238Xhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85085394136&doi=10.1007%2fs12325-020-01378-y&partnerID=40&md5=294bf86e41a2d61f16f722316434b07ahttps://scholars.lib.ntu.edu.tw/handle/123456789/580025Background: No trials have compared cabozantinib and regorafenib for the second-line treatment of advanced hepatocellular carcinoma (HCC). Objectives: Conduct a matching-adjusted indirect comparison (MAIC) of the efficacy and safety of second-line cabozantinib and regorafenib in patients with advanced HCC and disease progression after prior sorafenib. Methods: The CELESTIAL and RESORCE trials were used for indirect comparison of second-line cabozantinib and regorafenib in advanced HCC. Population-level data were available for RESORCE, individual patient data (IPD) for CELESTIAL. To align with RESORCE, the CELESTIAL population was limited to patients who received first-line sorafenib only. To minimize potential effect-modifying population differences, the CELESTIAL IPD were weighted to balance the distribution of clinically relevant baseline characteristics with those of RESORCE. Overall survival (OS) and progression-free survival (PFS) were evaluated for the matching-adjusted second-line CELESTIAL population and compared with those for RESORCE using weighted Kaplan-Meier curves and parametric modeling. Rates of grade 3/4 treatment-emergent adverse events (TEAEs) affecting > 5% of patients in any study arm were compared. Results: In the matching-adjusted second-line populations (CELESTIAL, effective sample size = 266; RESORCE, n = 573), median (95% confidence interval) OS was similar for cabozantinib and regorafenib (11.4 [8.9–17.0] versus 10.6 [9.1–12.1] months; p = 0.3474, log-rank test). Median PFS was longer for cabozantinib than regorafenib (5.6 [4.9–7.3] versus 3.1 [2.8–4.2] months; p = 0.0005, log-rank test). There was a trend for lower rates of some grade 3/4 TEAEs with regorafenib than with cabozantinib, which may reflect the exclusion of sorafenib-intolerant patients from RESORCE but not from CELESTIAL, a difference that the MAIC methods could not remove. Only diarrhea rates were statistically significantly lower for regorafenib (p ? 0.001). Conclusions: Cabozantinib may achieve similar OS and prolonged PFS compared with regorafenib in patients with progressive advanced HCC after prior sorafenib. ? 2020, The Author(s).Cabozantinib; CELESTIAL; Hepatocellular carcinoma (HCC); Indirect treatment comparison; Matching-adjusted indirect comparison (MAIC); Regorafenib; RESORCE; Second-line; Systemic therapy; Targeted therapy[SDGs]SDG3alpha fetoprotein; cabozantinib; placebo; regorafenib; sorafenib; angiogenesis inhibitor; anilide; antineoplastic agent; cabozantinib; carbanilamide derivative; pyridine derivative; regorafenib; adult; advanced cancer; aged; Article; cancer fatigue; cancer grading; cancer growth; cancer therapy; comparative effectiveness; controlled study; diarrhea; disease exacerbation; drug efficacy; drug safety; female; hand foot syndrome; human; hypertension; Kaplan Meier method; liver cell carcinoma; major clinical study; male; middle aged; overall survival; patient coding; practice guideline; progression free survival; skin manifestation; systemic therapy; cancer staging; liver tumor; pathology; randomized controlled trial (topic); Angiogenesis Inhibitors; Anilides; Antineoplastic Agents; Carcinoma, Hepatocellular; Comparative Effectiveness Research; Disease Progression; Female; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Outcome and Process Assessment, Health Care; Phenylurea Compounds; Progression-Free Survival; Pyridines; Randomized Controlled Trials as Topic; Sorafenibjournal article10.1007/s12325-020-01378-y324248052-s2.0-85085394136