1. Comparative Efficacy of Cabozantinib and Regorafenib for Advanced Hepatocellular Carcinoma
- Author
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Kelley, Robin K, Mollon, Patrick, Blanc, Jean-Frédéric, Daniele, Bruno, Yau, Thomas, Cheng, Ann-Lii, Valcheva, Velichka, Marteau, Florence, Guerra, Ines, and Abou-Alfa, Ghassan K
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Digestive Diseases ,Clinical Trials and Supportive Activities ,Liver Cancer ,Cancer ,Clinical Research ,Liver Disease ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,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 ,Sorafenib ,CELESTIAL ,Cabozantinib ,Hepatocellular carcinoma ,Indirect treatment comparison ,Matching-adjusted indirect comparison ,RESORCE ,Regorafenib ,Second-line ,Systemic therapy ,Targeted therapy ,Pharmacology and Pharmaceutical Sciences ,General Clinical Medicine ,Clinical sciences ,Pharmacology and pharmaceutical sciences - Abstract
BackgroundNo trials have compared cabozantinib and regorafenib for the second-line treatment of advanced hepatocellular carcinoma (HCC).ObjectivesConduct 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.MethodsThe 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.ResultsIn 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).ConclusionsCabozantinib may achieve similar OS and prolonged PFS compared with regorafenib in patients with progressive advanced HCC after prior sorafenib.
- Published
- 2020