A bidirectional cohort study of chemotherapy-targeted alternating therapy on outcomes of third-line metastatic colorectal cancer.

e15607 Background: CSCO guidelines recommend trifluridine/tipiracil (TAS-102) plus bevacizumab as standard third-line therapy for metastatic colorectal cancer (mCRC). An alternating strategy combining TAS-102 with small-molecule anti-angiogenic agents has emerged in practice but lacks real-world evidence. This study compared TAS-102+regorafenib group (REG) with TAS-102+bevacizumab group (BEV). Methods: This single-center bidirectional cohort included patients initiating TAS-102-based third-line therapy. Patients received TAS-102+REG (TAS-102 35 mg/m², Maximum single dose: 80 mg, orally, bid, days 1–5; REG 80–120 mg, orally, qd, days 6–15, repeated every 15 days) or TAS-102+BEV (Recommended dosing regimen per guidelines). Primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints were time to treatment discontinuation (TTD) and adverse events (AEs). Outcomes were analyzed using Kaplan–Meier, log-rank tests, and Cox models. Results: Fifty-one patients were enrolled (REG n = 30; BEV n = 21). Median follow-up was 390 days (95% CI 232–441). Median PFS was 199 days（95% CI 165.46-232.54） vs 125 days（95% CI 84.68-165.32）, median OS 584 days（95% CI 388.75-NR）vs 322 days（95% CI 34.74-NR）, and median TTD 149 days（95% CI 80.13–217.87） vs 232 days（95% CI 198.01–265.99）for REG and BEV, respectively. Median PFS was prolonged in the REG group compared with the BEV group (199 vs. 125 days). No significant differences were observed (PFS p = 0.084; OS p = 0.831; TTD p = 0.294). Cox analysis showed an HR for PFS of 0.55 (95% CI 0.28–1.09; p = 0.088), suggesting a trend toward reduced progression risk with REG. HRs for OS and TTD were 0.89 (95%CI 0.30–2.66, p = 0.83) and 1.49 (95%CI 0.70–3.14, p = 0.30). AE incidence was 76.4% (REG) and 71.4% (BEV). Grade ≥3 AEs were infrequent (6.7% vs 9.5%). Myelosuppression was more common with REG (56.6% vs 38%), while fatigue was the most frequent AE in both groups (33.3% vs 23.8%).20% of the REG group had hypertension and 14.2% of the BEV group had nausea, all grade 1–2. Conclusions: No statistically significant differences in PFS, OS or TTD were found among TAS-102-based regimens in this study. Nevertheless, TAS-102+regorafenib group was preliminarily shown to have at least equivalent efficacy to TAS-102+bevacizumab group in real-world practice with potential advantages, which deserves further verification in large prospective studies.