point of this assessment, it that weekly LFT was estimated that overall monitoring should around 30,000 patients have occur for any patient been exposed to regorafenib with elevated LFTs or (Stivarga) commercially. This any patient with any post-marketing reporting degree of hepatic frequency (6/30,000) is impairment. considered in line with This recommendation liver injury’ being ‘Severe is in concordance with reflected as uncommon ADR the FDA and (with reported fatal publications issued by outcomes) within the label. Bayer and Onyx An ongoing open-label Phase Pharmaceuticals. IIIb study in patients treated with metastatic CRC who have progressed after standard therapy was developed to provide regorafenib to subjects diagnosed with metastatic colorectal cancer who have failed all approved standard therapies. The study with nearly 3000 enrolled CRC patients will also further evaluate the incidence and severity of liver function abnormalities, as well as label-defined liver function monitoring schedule and associated dose modification (dose interruptions and dose reductions) scheme to address the safety concerns for severe drug-induced liver injury as outlined in the EURMP v2.5 (see M1.13.1). So far, data on hepatotoxicity from the CONSIGN trial does not preclude the current label defined LFT monitoring recommendation. At present, one case of severe liver injury has been observed in this study only (see case [information redacted] in Appendix 6 of section 1 within Appendix B of Module 2.7.4 provided with the GIST submission). A hepatotoxicity profile comparable to the one observed in CRC was confirmed for the GIST indication (see also section
point of this assessment, it was estimated that overall around 30,000 patients have been exposed to regorafenib (Stivarga) commercially. This post-marketing reporting frequency (6/30,000) is considered in line with ‘Severe liver injury’ being reflected as uncommon ADR (with reported fatal outcomes) within the label. An ongoing open-label Phase IIIb study in patients treated with metastatic CRC who have progressed after standard therapy was developed to provide regorafenib to subjects diagnosed with metastatic colorectal cancer who have failed all approved standard therapies. The study with nearly 3000 enrolled CRC patients will also further evaluate the incidence and severity of liver function abnormalities, as well as label-defined liver function monitoring schedule and associated dose modification (dose interruptions and dose reductions) scheme to address the safety concerns for severe drug-induced liver injury as outlined in the EURMP v2.5 (see M1.13.1). So far, data on hepatotoxicity from the CONSIGN trial does not preclude the current label defined LFT monitoring recommendation. At present, one case of severe liver injury has been observed in this study only (see case [information redacted] in Appendix 6 of section 1 within Appendix B of Module 2.7.4 provided with the GIST submission). A hepatotoxicity profile comparable to the one observed in CRC was confirmed for the GIST indication (see also section that weekly LFT monitoring should occur for any patient with elevated LFTs or any patient with any degree of hepatic impairment. This recommendation is in concordance with the FDA and publications issued by Bayer and Onyx Pharmaceuticals.