Background: FIRE-3 compared first-line therapy with FOLFIRI plus either cetuximab or bevacizumab in 592 KRAS exon 2 wild-type mCRC patients. We analyzed the efficacy dependent on gender and primary tumor location within the RAS wild-type population (n=342). Methods: Primary tumor location was defined as follows: right sided CRC (RCRC): coecum to hepatic flexure; left sided CRC (LCRC): splenic flexure to rectum. Colon transversum tumors (n=9) were excluded. Differences in response (ORR) and survival (PFS/OS) within both treatment arms were calculated using two-sided Fisher´s exact and logrank test, respectively. Results: In location wise comparison LCRC shows better efficacy results (ORR, PFS and OS) when compared with RCRC especially in the cetuximab arm (Table). Female gender has a trend towards lower tumor response rates, shorter PFS and OS when compared to male patients. Conclusions: MCRC is a heterogeneous disease. Treatment efficacy depends on primary tumor location and patients’ gender. Effects were more prominent in patients receiving FOLFIRI plus cetuximab where male patients with LCRC tumors are favored.

Abbreviations: Bev, bevacizumab; Cet, cetuximab; OR, Odds ratio; HR, hazard ratio; mo, months. *= logrank p; ^#= two-sided Fisher’s exact p.