Predictive factors for early mortality after regorafenib or trifluridine/tipiracil initiation in metastatic colorectal cancer

BACKGROUND: Regorafenib and trifluridine/tipiracil (FTD/TPI) are standard later-line treatments for patients with refractory metastatic colorectal cancer. However, these drugs show limited efficacy in some patients, and inappropriate use may increase toxicity and reduce quality of life. This study aimed to identify clinical predictors of early mortality after regorafenib or FTD/TPI initiation. METHODS: We retrospectively analyzed patients enrolled in the multicenter REGOTAS study. Early mortality was defined as death within 12 weeks of treatment initiation. Variables with P < .05 in univariate analysis were entered into a multivariable Cox model for overall survival (OS). Patients alive at 15 weeks (a 3-week margin beyond 12 weeks) were censored. RESULTS: We analyzed 523 patients (regorafenib, N = 212; FTD/TPI, N = 311). Independent predictors of early mortality were Eastern Cooperative Oncology Group performance status (≥1), low albumin level (<3.5 g/dL), high C-reactive protein level (≥1.0 mg/dL), and short time from first-line chemotherapy initiation (<18 months). The high-risk group (patients with all four factors, N = 35) showed higher mortality and shorter OS than the low-risk group (others, N = 488): 12-week mortality rate 40% vs 14%, 14-week mortality rate 60% vs 18%, and median OS: 2.8 months vs 7.8 months (hazard ratio: 3.52; P-value < .0001). CONCLUSION: Our predictive model may help identify patients at high risk of early mortality after regorafenib or trifluridine/tipiracil initiation and support shared decision-making between clinicians and patients regarding further chemotherapy or best supportive care.