Real-World Analysis of Irinotecan With or Without Fluorouracil in the Second-Line Treatment of Metastatic Colorectal Cancer

Background: The most used first-line chemotherapy backbone for metastatic colorectal cancer (mCRC) is fluoropyrimidine and oxaliplatin. Despite limited data supporting the superiority of second-line FOLFIRI over irinotecan, guidelines continue to endorse both options, and FOLFIRI remains more commonly used. Patients and Methods: This study used a nationwide electronic health record–derived deidentified database to select patients with mCRC who received first-line treatment with fluoropyrimidine and oxaliplatin with or without a biologic agent, and second-line treatment with irinotecan ± fluorouracil with or without a biologic agent. The Kaplan-Meier method was used to estimate survival outcomes, and the Cox proportional hazards model was used for univariable and multivariable analyses (MVA). Results: A total of 3,215 patients met the eligibility criteria for inclusion in the analysis. In the second-line setting, FOLFIRI was the most commonly used chemotherapy backbone (90.6% vs 9.4% for irinotecan). Most patients also received a biologic agent, and those who received FOLFIRI were younger and had better ECOG performance status. There was no difference in first-line treatment duration or second-line irinotecan dose intensity between the FOLFIRI and irinotecan cohorts. Overall survival (OS) was longer with FOLFIRI than with irinotecan (median, 14.4 vs 9.8 months; P <.0001), as were time to treatment discontinuation and time to next treatment. In MVA, when controlling for age, ethnicity, stage at diagnosis, number of comorbidities, CEA level, ECOG performance status, and first-line treatment, irinotecan was associated with shorter OS than FOLFIRI (hazard ratio, 1.36; P <.001). In MVA, the addition of a biologic agent to FOLFIRI and irinotecan prolonged survival outcomes in some subgroups. No difference in OS was observed in patients treated with irinotecan and a biologic agent compared with those treated with FOLFIRI. Conclusions: In this large, retrospective, real-world analysis, FOLFIRI was associated with longer OS than irinotecan in the second-line treatment of mCRC when controlling for important covariates. These findings appear to support the continued use of FOLFIRI as the chemotherapy backbone in second-line treatment of mCRC for most patients, although combining irinotecan with a biologic agent may offer comparable efficacy.