Clin Oncol (R Coll Radiol). 2026 May 5;55:104186. doi: 10.1016/j.clon.2026.104186. Online ahead of print.
ABSTRACT
AIM: Third-line treatment options for metastatic colorectal cancer (mCRC) remain limited. Chemotherapy rechallenge has shown efficacy in this setting, but direct comparisons with tyrosine kinase inhibitors (TKIs) are lacking. This real-world study aimed to retrospectively compare TKI (regorafenib/fruquintinib) versus rechallenge chemotherapy in refractory mCRC.
MATERIALS AND METHODS: From April 2018 to June 2023, 107 mCRC patients receiving third-line therapy were analyzed (median follow-up: 6.6 months). Endpoints included overall survival (OS) and progression-free survival (PFS). Patients were divided into TKI (n = 53) and rechallenge chemotherapy (n = 54) groups. Kaplan-Meier curves, Cox models, and RECIST 1.1-based spider/waterfall plots were generated using RStudio (R Foundation for Statistical Computing, Vienna, Austria) 3.5.2 (significance: P < .05).
RESULTS: Rechallenge chemotherapy significantly improved OS (hazard ratio [HR] = 0.44, 95% CI = 0.27-0.70; P < .001) and PFS (HR = 0.58, 95% CI = 0.27-0.70; P = .002) with significantly higher objective response rate (10.9% vs. 0%, P = .025) and disease control rate (67.4% vs. 52.8%, P = .090) compared to TKIs.
CONCLUSION: In this single-center retrospective real-world cohort, rechallenge chemotherapy was associated with improved survival and response outcomes compared with TKIs in third-line mCRC. However, given the non-randomized design and potential confounding, these findings should be considered hypothesis-generating. Rechallenge chemotherapy may be considered in selected patients with prior chemotherapy sensitivity and an adequate treatment-free interval, pending prospective validation.
PMID:42258990 | DOI:10.1016/j.clon.2026.104186
