CLINICAL-MOLECULAR DETERMINANTS OF THE BENEFIT OF OXALIPLATIN RE-CHALLENGE IN PATIENTS WITH CHEMO-REFRACTORY METASTATIC COLORECTAL CANCER (MCRC)

BACKGROUND: Oxaliplatin is a backbone cytotoxic treatment for mCRC patients, particularly in the front-line setting. In the refractory disease, current treatment options are scarce and with limited efficacy. In Brazil, given limited access to regorafenib or trifluridine and tipiracil, OxRe may be an alternative for fit patients. However, more evidence is needed to determine which patients do benefit from this treatment strategy. METHODS: We retrospectively explored the Oncoclinicas Data Lake for patients with mCRC treated with oxaliplatin in the first- or second-line setting followed by at least one chemotherapy regimen free of oxaliplatin (different from maintenance with 5FU/LV or capecitabine) and re-exposure to oxaliplatin in third-or fourth-line between 2015 and 2021. We analyzed the impact of different clinical-molecular features and addition of bevacizumab (Bev) to oxaliplatin-based rechallenge in uni- and multivariable prognostic models. RESULTS Out of 4,317 patients with mCRC, 157 (4%) were treated with OxRe. The median age was 50 years, 65% were female, 38% were stage IV at diagnosis and 43% had known RAS/BRAF wild-type status. Concomitant Bev in front-line line was administered in 23% of the patients, and 38% received Bev at the time of OxRe. Median oxaliplatin-free interval (from front-line to rechallenge) was 15 months. Median overall survival (OS) after OxRe was 12 months (CI95% 1015) and median time to treatment discontinuation (TTD) of the OxRe was 3.4 months (CI95% 2.8-4.2). In the univariate analysis, statistically significant (P<0.1) associations were seen for longer TTD at OxRe in patients without prior exposure to Bev in front-line (3.5 vs. 1.9 months) in case of Bev administration in rechallenge setting (3.9 vs. 2.8. months), in patients whose tumors were RAS/BRAF wildtype (3.8 vs. 2.9 months). In multivariable model, the only independent prognostic factor was addition of Bev to OxRe (P=0.036). Interestingly, 31% of all patients had median TTD > 6 months, largely enriched (65%) in patients with first Bev exposure at the time of OxRe. CONCLUSIONS: A small proportion of patients with mCRC are eligible to OxRe in a large real-world cohort. Our study suggests that concomitant use of Bev is associated with better outcomes in refractory mCRC patients retreated with oxaliplatin-based therapy. One-third of the patients are long-term responders (TTD > 6 months), reinforcing the value of the strategy in carefully selected patients.