Accumulation of Metabolite M-2 Predicts Overall Survival of Chemorefractory Metastatic Colorectal Cancer Patients Treated with Regorafenib (Stivarga®) Interview with:
Joseph Germino, M.D., PhD
Vice President US Medical Affairs Oncology
Bayer Healthcare Pharmaceuticals
Whippany, N.J. 07981 What is the background for this study? What are the main findings?

Response: Regorafenib is an oral multi-kinase inhibitor that potently blocks multiple protein kinases involved in tumor angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF), metastasis (VEGFR3, PDGFR, FGFR) and tumor immunity (CSF1R).

This prospective pharmacokinetic (PK) ancillary study is part of a prospective phase II study evaluating treatment response with regorafenib in patients with chemorefractory metastatic colorectal cancer (mCRC) called TEXAN, which aimed to investigate correlations between overall survival (OS) and regorafenib, or its enterohepatic cycle-dependent active metabolites M-2 and M-5 concentrations.

As measured by LC-MS/MS, the main findings showed that regorafenib, M-2 and M-5 were respectively 1.99 (1.03-2.73), 1.44 (0.89-2.49) and 1.61 (0.79-2.37) mg/L during the first cycle at day 15 (C1D15) and 1.90 (1.10-2.76), 1.29 (0.77-2.24) and 1.17 (0.45-2.42) mg/L at during the second cycle at day 15 (C2D15). What should readers take away from your report?

Response: The prospective study showed a dramatic overall survival benefit in patients accumulating M-2 (HR=0.35 (0.14-0.86), p-value=0.0226), which was confirmed in further analyses with an independent 66% reduction in risk of death in the group of 55 patients. What recommendations do you have for future research as a result of this work?

Response: The study brought valuable insights into how the body handles regorafenib and its active metabolites. These results and continued research may help to develop individual regorafenib dosage modification strategies based on pharmacokinetic monitoring.

Disclosures: Joseph Germino, M.D. is the vice president of medical affairs, oncology at Bayer. 


ASCO 2019 Abstract #3121: Accumulation of active metabolite M-2 predicts overall survival (OS) of chemorefractory metastatic colorectal cancer patients treated with regorafenib (REGO)

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Last Updated on June 5, 2019 by Marie Benz MD FAAD