KDR gene as a Predictive Biomarker of Response to Regorafenib in Patients with Metastatic Colorectal Cancer (mCRC)

Background: Regorafenib is an oral diphenyl urea multikinase inhibitor which is anti- angiogenic, and has shown promising anti-tumor activity in Metastatic Colorectal Cancer (mCRC). Reports have shown that response to regorafenib is more favourable in patients with KDR gene mutation. This study correlates KDR gene mutation as an ideal predictive biomarker to regorafenib (Tyrosine Kinase Inhibitor) response in metastatic colorectal cancer (MCRC). Methods: This is a single centre prospective analysis of total 9 patients at HCG cancer speciality centre, Bengaluru, India. The median age of 9 patients was 54 years (21-71 years). 5 patients were male and 4 patients were female, 6 patients are African and 3 were Indian. KRAS gene was found to be mutated in 6 patients and wild type in 3 patients. Out of 9 patients, 6 have received FOLFOX-4 chemotherapy+Biological for 6 cycles and 3 patients received FOLFIRI chemothearpy+Biological for 3 cycles as 1st line treatment. These patients received tab Regorafenib as 3rd line treatment. For all patients 48 Gene panel was done, which includes extended RAS and KDR gene mutation analysis. Results: Analysis at the end of 3 months of treatment, 2 patients had PR, 1 patient had SD, 5 patients had PD and 1 patient defaulted. There was no correlation of response with KRAS mutational status. KDR (VEGFR-2) was wild type in all the patients. With regards to safety, the drug was well tolerated by all patients and no one withdrawn because of adverse effects. Conclusions: Absence of KDR gene mutation may not respond to regorafenib treatment in MCRC. To predict KDR gene mutation as a biomarker, large number of studies with mutated KDR gene is required.