612P - Updated results from the multicenter phase II study of fruquintinib plus mFOLFOX6/FOLFIRI as first-line therapy in advanced metastatic colorectal cancer (mCRC)

Background

The fruquintinib (a highly selective, and potent oral inhibitor of VEGF receptor 1, 2, 3) plus mFOLFOX6/FOLFIRI (standard chemotherapy) in patients (pts) with advanced mCRC study was a prospective, open-label, multi-center, single-arm phase 2 study (NCT05004441). The results of this study have been previously reported at the 2023 ASCO GI (152 Poster Session) and here we updated the efficacy and safety results with more enrolled pts and longer follow-up duration.

Methods

Pts aged 18-75 years with unresectable or metastatic CRC, without prior systemic threatment were recruited. RAS/BRAF status should be detected to exclude BRAF mutations before enrollment. Pts received fruquintinib (3mg, QD, PO, Q4W) in combination with mFOLFOX6/FOLFIRI (Q2W) for up to 8 cycles. Pts with SD or above were 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 was ORR, secondary endpoints included DCR, PFS, OS and safety.

Results

At updated analysis (cutoff: April 20, 2023), 37 pts were enrolled (median age 56, 18 males, 6 with right half colon cancer, 15 harboring RAS mutations, 18 with liver metastases). For 30 pts who were in efficacy analysis, 23 achieved PR (76.67%), 6 achieved SD (20%), resulting in an ORR of 76.67% and a DCR of 96.67%. At a median follow-up of 7.49 mo, 2 pts underwent surgical resection, 21 pts were still in treatment, and median PFS had not yet reached. Safety profile exhibited that the regimen was tolerable and mainly grade 1/2. Grade 3 TRAEs were neutrophil count decreased (23.33%), leukopenia (10%), GGT increased and hypertension accounted for 6.67% respectively, AST increased (3.33%). No pts have serious adverse events.

Conclusions

Updated analysis of this study data further support current combination therapy with fruquintinib plus mFOLFOX6/FOLFIRI as the first-line therapy followed by fruquintinib plus capecitabine maintenance for advanced mCRC pts, which shows durable response and a favorable long-term safety profile. The study is still ongoing.

Clinical trial identification

NCT05004441.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.