Efficacy and safety of fruquintinib plus investigator's choice of chemotherapy as second-line therapy in metastatic colorectal cancer: Updated results of a multicenter, single-arm, phase 2 trial.

3571 Background: Fruquintinib, a potent and highly selective vascular endothelial growth factor receptor (VEGFR) inhibitor, combined with investigator’s choice of chemotherapy as second-line therapy in patients (pts) with metastatic colorectal cancer (mCRC) showed promising efficacy in preliminary analysis (2023 ASCO Poster-3582) of the prospective, open-label, multicenter, single-arm phase 2 trial (ChiCTR2200059280). Here we reported the updated efficacy data. Methods: Pts with mCRC progressed after first-line prior systemic treatment were administered fruquintinib (5~3 mg, d1-21, q4w) and investigator’s choice of chemotherapy (fluorouracil ± irinotecan ± oxaliplatin, d1, q3w) for up to 8 cycles. Patients without disease progression (PD) were followed by fruquintinib maintenance until PD or unacceptable toxicities. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), overall survival (OS) and safety. Results: From November 2021 to November 2023, 100 pts were enrolled. Median age was 63 years (IQR, 56.5-71) and 61.0% were male. The left colon cancer involved in 77.0% pts. All pts had MSS/pMMR phenotype and 37.0% had RAS/BRAF-mutated tumors. 9.0% received prior anti-EGFR and 55.0% received anti-VEGF therapy. Most common sites of metastatic disease were liver (57.0%) and lung (41.0%). As of January 20, 2024, with a median follow-up of 9.3 mo, the median PFS was 6.9 mo (95%CI, 5.2-8.6), median OS was 20.1 mo (95%CI, 13.7-26.3). ORR was 26.0% (95%CI, 17.9-36.2), DoR was 11.3 mo (95%CI, 8.6-14.0), and DCR was 83.3% (95%CI, 74.0-89.9) in 96 efficacy-evaluable pts. The incidence of adverse events was comparable to the known toxicities associated with fruquintinib and chemotherapy. No treatment-related deaths occurred. Grade 3/4 adverse effects occurred in 33 pts (33.0%), and most commonly were neutropenia (21.0%), leukopenia (14.0%), thrombocytopenia (6.0%), proteinuria (5.0%), hypothyroidism (3.0%), diarrhea (2.0%), hand-foot syndrome (2.0%) and hypertension (1.0%). Conclusions: Fruquintinib combined with investigator’s chemotherapy followed by fruquintinib maintenance as second-line therapy showed satisfactory anti-tumor activity, prolonged PFS and OS, and manageable safety profiles in pts with mCRC. Further analysis of all pts with long-term follow-up will be presented in the future. Clinical trial information: ChiCTR2200059280.