Regorafenib versus Cabozantinib as a Second-Line Treatment for Advanced Hepatocellular Carcinoma: An Anchored Matching-Adjusted Indirect Comparison of Efficacy and Safety

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 ∼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

An open-label trial to assess the safety of regorafenib in Turkish patients with metastatic colorectal cancer (mCRC) that progressed on standard therapy (REGARD)

ESMO 17th World Congress on Gastrointestinal Cancer -- JUL 01-04, 2015 -- Barcelona, SPAINWOS: 000357047400123…ESM

Safety and efficacy of regorafenib in patients with treatment-refractory metastatic colorectal cancer in Turkey: the single-arm, open-label REGARD study

Yumuk, Perran Fulden/0000-0001-8650-299X; benekli, mustafa/0000-0003-3184-4946; Aykan, Nuri Faruk/0000-0002-5472-3218; Dane, Faysal/0000-0001-6584-902XWOS: 000527801000004PubMed: 32220908Objectives Regorafenib improved overall survival in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies in two randomised, phase III trials, but has not been evaluated in Turkey. REGARD evaluated the safety and efficacy of regorafenib in Turkish patients with treatment-refractory mCRC. Design Open-label, single-arm, phase IIIb study conducted between July 2013 and April 2015. Setting 11 tertiary centres in Turkey. Participants Eligible patients were adults with mCRC who had disease progression within 3 months after receiving their last dose of approved standard therapies and who had an Eastern Cooperative Oncology Group performance status = 3 TEAE. the most common grade >= 3 regorafenib-related TEAEs were hypophosphataemia (11%), fatigue (8%), hyperbilirubinaemia (6%), hand-foot skin reaction (5%), hypertension (5%), anorexia (5%) and increased alanine aminotransferase (5%). TEAEs led to dose reduction in 30% of patients. Regorafenib-related TEAEs led to treatment discontinuation in 17% of patients. Median PFS was 3.1 months (95% CI 2.9 to 3.8). Conclusion the regorafenib safety profile and PFS in REGARD were consistent with the results of previous trials of regorafenib in mCRC. Regorafenib is an option for patients in Turkey with treatment-refractory mCRC.BayerBayer AGThis work was supported by Bayer. Bayer provided the study medication and collaborated with the authors to design the study. Bayer worked with the investigators on the collection, analysis and interpretation of the data, and on the preparation of this report. the authors made the final decision to submit the article for publication

Supplementary Material for: Regorafenib vs. cabozantinib as second-line treatment for advanced hepatocellular carcinoma: an anchored matching-adjusted indirect comparison of efficacy and safety

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 ~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 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 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, 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

An open-label trial to assess the safety of regorafenib in Turkish patients with metastatic colorectal cancer (mCRC) that progressed on standard therapy (REGARD)

ESMO 17th World Congress on Gastrointestinal Cancer -- JUL 01-04, 2015 -- Barcelona, SPAINWOS: 000357047400123ESM

Safety and efficacy of regorafenib in patients with treatment-refractory metastatic colorectal cancer in Turkey: the single-arm, open-label REGARD study

Objectives Regorafenib improved overall survival in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies in two randomised, phase III trials, but has not been evaluated in Turkey. REGARD evaluated the safety and efficacy of regorafenib in Turkish patients with treatment-refractory mCRC