Outcomes for FOLFIRI plus bevacizumab or cetuximab in patients treated with oxaliplatin-based adjuvant therapy: A combined analysis of FIRE-3 and CALGB/SWOG 80405 (Alliance).

BACKGROUND: Metastatic recurrence of colorectal cancer (mCRC) after adjuvant therapy may differ biologically from recurrence in untreated mCRC. We examined first-line treatment outcomes of patients within the phase III CALGB/SWOG 80405 (CALGB 80405) and FIRE-3 trials according to previous exposure to oxaliplatin-based adjuvant treatment. METHODS: Patients from CALGB 80405 primary analysis (N = 1131) and FIRE-3 intent-to-treat population (N = 592) treated with FOLFIRI who previously received either oxaliplatin-based adjuvant therapy or no adjuvant therapy were identified. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared using the log-rank test. Adjusted Cox regression models were used to compare outcomes according to biologic agent and prior adjuvant treatment. RESULTS: A total of 800 patients were included in the analysis. There were no significant differences in OS and PFS based on adjuvant treatment. Among patients who received adjuvant oxaliplatin-based chemotherapy (N = 123), median PFS was 11.5 months for FOLFIRI-bevacizumab (bev) and 10.1 months for FOLFIRI-cetuximab (cet) (adjusted HR [95 %CI] = 0.81 [0.56, 1.18], p = 0.27). Median OS in the same group was 41.0 months for bev- vs 28.5 months for cet-treated patients (adjusted HR 95 %CI] = 0.78 [0.51, 1.20], p = 0.26). No significant interaction between treatment arm and prior adjuvant treatment was identified. CONCLUSIONS: No statistically significant difference in either OS or PFS by biologic agent was found in this unplanned subset analysis of two large, randomized phase III trials. However, further investigation is warranted to evaluate possible survival differences in larger patient cohorts.

Duke Scholars

Author Donna Niedzwiecki Biostatistics & Bioinformatics, Division of Biostatistics