Effect of trifluridine/tipiracil in patients treated in RECOURSE by prognostic factors at baseline: an exploratory analysis

BACKGROUND: The choice of treatment in patients with metastatic colorectal cancer (mCRC) is generally influenced by tumour and patient characteristics, treatment efficacy and tolerability, and quality of life. Better patient selection might lead to improved outcomes. METHODS: This post hoc exploratory analysis examined the effect of prognostic factors on outcomes in the Randomized, Double-blind, Phase 3 Study of trifluridine tipiracil (FTD/TPI) plus Best Supportive Care (BSC) versus Placebo plus BSC in Patients with mCRC Refractory to Standard Chemotherapies (RECOURSE) trial. Patients were redivided by prognosis into two subgroups: those with <3 metastatic sites at randomisation (low tumour burden) and ≥18 months from diagnosis of metastatic disease to randomisation (indolent disease) were included in the good prognostic characteristics (GPC) subgroup; the remaining patients were considered to have poor prognostic characteristics (PPC). RESULTS: GPC patients (n=386) had improved outcome versus PPC patients (n=414) in both the trifluridine/tipiracil and placebo arms. GPC patients receiving trifluridine/tipiracil (n=261) had an improved median overall survival (9.3 vs 5.3 months; HR (95% CI) 0.46 (0.37 to 0.57), p<0.0001) and progression-free survival (3.3 vs 1.9 months; HR (95% CI) 0.56 (0.46 to 0.67), p<0.0001) than PPC patients receiving trifluridine/tipiracil (n=273). Improvements in survival were irrespective of age, Eastern Cooperative Oncology Group Performance Status (ECOG PS), KRAS mutational status, and site of metastases at randomisation. In the trifluridine/tipiracil arm, time to deterioration of ECOG PS to ≥2 and proportion of patients with PS=0–1 discontinuing treatment were longer for GPC than for PPC patients (7.8 vs 4.2 months and 89.1% vs 78.4%, respectively). CONCLUSION: Low tumour burden and indolent disease were factors of good prognosis in late-line mCRC, with patients experiencing longer progression-free survival and greater overall survival.