A multi-cohort real-world study of treatment for metastatic colorectal cancer (mCRC): Overall efficacy analysis and subgroup analysis of previous bevacizumab use or not.

e15530 Background: Fruquintinib (Fru) is a VEGFR1/2/3 inhibitor and has been approved in USA for third-line treatment of mCRC based on FRESCO-2 data. Regorafenib (Reg) and TAS-102 have shown promise in mCRC treatment. This study evaluated the efficacy of Fru, Reg (monotherapy or in combination with immune checkpoint inhibitors, ICIs), and TAS-102 plus Bev in mCRC and in a subgroup analysis with or without prior Bev therapy. Methods: This study included patients with mCRC who received Fru/Reg mono, Fru/Reg plus ICIs, or Bev plus TAS-102. Patients were over 18 years old, had histologically confirmed mCRC, ECOG PS 0-1, and had received ≥2 previous standard therapies. The study assessed overall survival (OS) and progression-free survival (PFS). Results: A total of 418 patients from 3 cohorts were included：Cohort 1 (168 patients) received Fru mono (98 patients) and Reg mono (70 patients), of which 62 (63.27%) and 27 (38.57%) patients previously received Bev. Cohort 2 (171 patients) received Fru plus ICIs (104 patients) and Reg plus ICIs (67 patients), of which 73 (70.19%) and 54 (80.60%) patients previously received Bev. Cohort 3 (183 patients) received Fru plus ICIs (104 patients) and TAS102 plus Bev (79 patients), of which 73 (70.19%) and 63 (79.75%) patients previously received Bev. In cohort 1, compared with Reg mono, Fru mono showed a statistically significant difference in mPFS efficacy in overall patients (mPFS: 3.83 versus 2.53 months, p = 0.00015, HR: 0.544, 95%CI: 0.396-0.748) and in patients previously treated with Bev (mPFS: 3.98 versus 2.70 months, p = 0.0019, HR: 0.485, 95%CI: 0.305-0.772). Compared with patients who received Reg mono, there was a trend toward improved OS in patients receiving Fru mono. In cohort 2, compared with Reg plus ICIs, Fru plus ICIs significantly improved OS (mOS: 17.43 versus 13.92 months, p = 0.0081, HR: 0.588, 95%CI: 0.395-0.875). In the subgroup analysis of previous Bev treatment or not, Fru plus ICIs showed a trend of benefit in both mPFS and mOS. In cohort 3, compared with TAS-102 plus Bev, mOS and mPFS were significantly improved in Fru plus ICIs, both in the overall patients (mPFS: 5.95 versus 2.66 months, p＜0.0001, HR: 0.473, 95%CI: 0.349-0.640; mOS: 17.43 versus 8.97 months, p＜0.0001, HR: 0.468, 95%CI: 0.318-0.689) and in the subgroup analysis with (mPFS: 5.95 versus 3.02 months, p = 0.000078, HR: 0.557, 95%CI: 0.394-0.788; mOS: 17.43 versus 11.40 months, p = 0.0083, HR: 0.547, 95%CI: 0.347-0.862) or without (mPFS: 5.98 versus 2.20 months, p＜0.001, HR: 0.204, 95%CI: 0.102-0.410; mOS: NA versus 5.27 months, p = 0.00026, HR: 0.268, 95%CI: 0.126-0.570) Bev treatment. Conclusions: The results suggest that Fru-based regimens, particularly in combination with ICIs, may offer survival benefits compared to standard regimens, especially in patients without prior Bev use.