Efficacy and safety of fruquintinib plus mFOLFOX6/FOLFIRI as first-line therapy in advanced metastatic colorectal cancer (mCRC).

Abstract

152 Background: Fruquintinib is a highly selective, and potent oral inhibitor of VEGF receptor 1, 2, 3 and has been recommended as a third-line treatment for mCRC patients (pts) in China because of its low toxicity, favorable ORR and survival benefit. FOLFOX/FOLFIRI is the preferred chemotherapy regimens of first-line for mCRC pts according to the NCCN guideline. Our study aimed to investigate the efficacy and safety of fruquintinib plus mFOLFOX6/FOLFIRI as first-line therapy in advanced mCRC pts. Methods: In this prospective, open-label, multi-center, single-arm phase 2 study (NCT05004441), pts who are diagnosed with unresectable mCRC, without prior systemic threated are recruited. RAS/BRAF status should be detected to exclude BRAF mutations before enrollment. Pts receive fruquintinib (3mg, QD, PO, Q4W) in combination with mFOLFOX6/FOLFIRI (Q2W) for up to 8 cycles. Pts with SD or above are followed by maintenance therapy (fruquintinib 3mg, QD, PO, Q4W, capecitabine 850mg/m2, BID, PO, D1-7, D15-21, Q4W) until disease progression or intolerable toxicity. The primary endpoint is objective response rate (ORR), and secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Results: Based on a data cutoff of September 2, 2022, 19 pts have been enrolled and treated, of which 13 pts have efficacy evaluation data. Media age is 60 (range: 50-73) years and 62% pts are male. 7 (54%) pts harboring RAS mutations while the remaining pts are wild-type (wt). 54% treated with mFOLFOX6. At a median follow-up of 5.9mo, all 13 pts are still on treatment. In best overall response assessment, the ORR is 77%, with 10 (77%) partial response (PR). Stable disease (SD) is 3 (23%) with a DCR of 100%. Median PFS has not yet reached. Safety profile exhibited that the regimen is tolerable and mainly grade 1/2. Grade 3 treatment-related adverse events (TRAEs) are neutrophil count decreased (23%), GGT increased (15%), leukopenia, AST increased and hypertension accounted for 1% respectively. No pts have serious adverse events. Conclusions: Combination treatment with fruquintinib plus mFOLFOX6/FOLFIRI as the first-line therapy followed by fruquintinib plus capecitabine maintenance in advanced mCRC pts shows promising efficacy and manageable safety profile. Longer follow up data with PFS, and OS will be presented. Clinical trial information: NCT05004441 .