Sotorasib plus panitumumab and 5-fluorouracil in first-line treatment of patients with unresectable KRAS G12C mutated colorectal cancer unfit for a doublet/triplet chemotherapy: ENGIC 01 - PRODIGE 107 - FFCD 2306 - COLOSOTO trial.

INTRODUCTION

5-fluorouracil (5-FU) ± targeted therapy is a standard of care in frail/elderly patients with an unresectable colorectal adenocarcinoma (CRC) in first-line setting. Panitumumab plus sotorasib combination (KRAS G12C inhibitor) are promising in advanced line in KRAS G12C-mutated CRC. Here we assess the safety and efficacy of 5-FU combination with panitumumab and sotorasib as first-line treatment in frail/elderly patients with unresectable KRAS G12C-mutated CRC.

METHODS

In this ENGIC 01 - PRODIGE 107 - FFCD 2306 - COLOSOTO multicenter, open-label, prospective single-arm phase II trial, the main inclusion criteria are adult patients with unresectable locally advanced or metastatic KRAS G12C-mutated CRC, unfit for a doublet/triplet chemotherapy. All patients will receive 5-FU plus panitumumab and sotorasib in 2-week-cycles until progression or intolerance. The primary endpoint is 8-months progression-free survival (PFS). The secondary endpoints include median PFS, disease control rate, time to progression, overall survival, best objective response rate, duration of response, safety profile, quality of life and geriatric assessment. A 70% 8-months PFS is expected (H0 <50%), and 37 patients will need to be included.

PERSPECTIVES: Treatment with 5-FU plus panitumumab and sotorasib could be a promising alternative to 5-FU ± targeted therapy in first-line setting in frail/elderly patients with unresectable KRAS G12C-mutated CRC.