KEY TAKEAWAYS
- The early phase II study aimed to investigate the efficacy and safety of fruquintinib plus capecitabine as 1L treatment in pts with mCRC.
- The primary endpoint was to determine DCR.
- Researchers noticed promising clinical activity and manageable toxicities; further investigation is ongoing.
The best approach for patients (pts) with metastatic colorectal cancer (mCRC) ineligible for intravenous chemotherapy remains unclear. Fruquintinib, a highly specific inhibitor of VEGFR1/2/3, is a standard therapy in pts with previously treated advanced mCRC.
Xin Wang and the team aimed to evaluate the efficacy and safety of fruquintinib plus capecitabine as first-line treatment in mCRC pts who were not candidates for intravenous chemotherapy.
They performed an inclusive analysis in a phase II, single-arm study (NCT04866108) where eligible pts had at least one measurable disease, ECOG PS 0-2, adequate organ function, and were unfit for intravenous chemotherapy. Patients received fruquintinib (4 mg QD, D1-14) plus capecitabine (825mg/m2 BID, D1-14) every 3 weeks until disease progression or unacceptable toxicity.
Simon’s 2-stage design was applied. If ≥11 of 14 pts in stage 1 reached disease control (DC), further 29 pts would be enrolled; otherwise, the enrollment would be discontinued. Primary endpoint was DCR (RECIST v1.1), secondary endpoints were ORR, PFS, OS and safety (NCI-CTCAE v5.0).
About 3 (21.4%) of pts had a partial response (PR) and 10 (71.4%) had stable disease (SD) as of January 30, 2024, allowing the study to proceed to the second stage. By April 4, 2024, 20 pts were enrolled with a median age of 76 years (range: 41-86), 66.7% male, and 55.6% with KRAS mutation. ECOG PS was 1 in 50% and 2 in 5.5%, with left colon tumors in 50.0% and rectal tumors in 44.4%. Liver metastasis was present in 44.4% of pts, and 22.2% had ≥2 metastatic sites.
In efficacy-evaluable pts, the objective response rate (ORR) was 20.0% (3/15), and disease control rate (DCR) was 93.3% (14/15). One patient achieved a progression-free survival (PFS) of 498 days, with 3 pts exceeding 365 days of PFS and still under treatment. Median PFS and overall survival (OS) were not reached, and 12 pts remained in treatment. All pts experienced treatment-related adverse events (TRAEs), primarily grade 1-2, with grade 3 TRAEs reported in 5 pts and no treatment-related deaths.
The study concluded with encouraging clinical activity and acceptable toxicities for fruquintinib plus capecitabine in pts with elderly mCRC ineligible for intravenous chemotherapy. Ongoing trials will provide further insights into its efficacy and safety.
The study was funded by Beijing Friendship Hospital.
Clinical Trial: https://www.clinicaltrials.gov/study/NCT04866108
Xin Wang, Zhigang Bai, 2024. “Efficacy and safety of fruquintinib plus capecitabine as first-line treatment in patients (pts) with advanced metastatic colorectal cancer (mCRC) ineligible for intravenous chemotherapy: Early outcome report of a two-stage, single armed, phase II study.” Presented at ESMO-GI 2024 (Abstract 46P).
