Comparative analysis of first-line therapy with fruquintinib plus chemotherapy versus standard therapy in advanced metastatic colorectal cancer (mCRC): A prospective cohort study compared with propensity score matching (PSM) cohort.

3591 Background: We have previously reported that fruquintinib plus mFOLFOX6/FOLFIRI as the first-line therapy followed by fruquintinib plus capecitabine maintenance (FRU regimens) for advanced mCRC patients (pts) showed durable response and a favorable safety profile in this prospective, open-label, multicenter, single-arm phase 2 study (NCT05004441). We retrospectively collected matching data of standard therapy (STD regimens: bevacizumab/cetuximab plus chemotherapy) as the first-line treatment to compare with longer follow-up data in this study. Methods: Pts diagnosed with unresectable or metastatic CRC pts excluded BRAF mutations (Mut) were enrolled to receive FRU regimens. We collected retrospective data that pts who met our eligibility criteria receiving STD regimens as historical control data. PSM was performed to adjust potential confounders between two regimens. PSM was conducted on the basis of 4 clinically relevant variables (tumor location, RAS/BRAF status, liver metastasis). Efficacy was recorded and compared. Safety from FRU regimens was calculated and reported as well. Results: From Jul 22, 2021 to May 30, 2023, 43 pts were enrolled (median age 57 range: 37-74, 27 male, 25 harboring RAS Mut, 26 with liver metastases) in FRU regimens. We retrospectively collected 63 pts received STD regimens with 38% (24/63) RAS Mut. There was no significant difference in the baseline between two regimens. Up to Jan 15, 2024, before applying the PSM, pts received FRU regimens were benefit with a higher ORR than STD regimens (83.33% vs 61.90%, p=0.018, OR=3.077, 95%CI: 1.181-8.017), especially RAS Mut pts (87.50% vs 58.33%, p=0.051). The median PFS was 16.76 mo (95%CI 12.25-18.6) in FRU regimens, which was significantly longer than 10.38 mo of STD regimens (p=0.0115). Favorable PFS was observed in RAS Mut pts received FRU regimens compared with STD regimens (14.16 mo vs 10.48 mo, p=0.1635). After 1:1.5 PMS, pts with FRU regimens showed a significantly improvement in median PFS compared with STD regimens (15.9mo vs 11.3mo, p=0.020, HR=0.472, 95%CI: 0.251-0.889). Safety profile exhibited the FRU regimens was tolerable and main TEAEs were grade 1/2. Most common grade 3/4 TEAEs were neutrophil count decreased (18.60%), leukopenia (16.28%) and lymphocytopenia (6.98%). Only one serious AE reported with gastric perforation recovered after non-operative therapy. Conclusions: The fruquintinib combination regimens as a first-line therapy for pts with mCRC significantly improved median PFS compared to standard treatment. Similar to the primary analysis, the safety profile was generally manageable with longer duration of treatment exposure. Fruquintinib combined with mFOLFOX6/FOLFIRI might be a more promising treatment option as first-line therapy for mCRC pts. Clinical trial information: NCT05004441 .