AML

Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer

In the October 10, 2020 edition of Journal of Clinical Oncology,  Chiara Cremolini and colleagues report on a patient level data overall survival analysis of FOLFOXIRI plus bevacizumab in advanced colorectal cancer. 

All clinical trials that had assessed the efficacy of FOLFOXIRI plus bevacizumab versus doublets + bevacizumab never utilized overall survival as a primary endpoint.  An individual patient data (IPD) meta-analysis was performed, to provide enough thyroid to determine the magnitude of overall survival with this treatment regimen.

PATIENTS AND METHODS

IPD from 5 eligible trials – CHARTA, OLIVIA , STEAM, TRIBE, and TRIBE2 was analyzed.  The primary end point was overall survival with secondary end points including progression-free survival (PFS), objective response rate (ORR), grade 3 and grade 4 adverse events, R0 resection rates, and subgroup analyses based off clinical and molecular characteristics.

1,697 patients were randomly assigned to FOLFOXIRI + bevacizumab (n = 846) or doublets + bevacizumab (n = 851). 78% had an ECOG of 0, and the median age was 61 years. After a median follow-up of 39.9 months, patients assigned to FOLFOXIRI + bevacizumab had significantly longer OS than those assigned to doublets + bevacizumab (median, 28.9 v 24.5 months; HR, 0.81; 95% CI, 0.72 – 0.91; P < .001), without any major heterogeneity between trials (P = .39; I2 = 2%).  There was no significant interaction effect between treatment arm and investigated characteristics was demonstrated. Patients who were assigned to FOLFOXIRI + bevacizumab had longer PFS (progression free survival median, 12.2 v 9.9 months; HR, 0.74; 95% CI, 0.67 to 0.82; P < .001), higher overall response rate (64.5% v 53.6%; P < .001), higher R0 resection rates (16.4% v 11.8%; P = .007), as well as higher rates of grade 3/4 neutropenia (45.8% v 21.5%; P < .001), febrile neutropenia (6.3% v 3.7%; P = .019), and diarrhea (17.8% v 8.4%; P < .001). The authors concluded “FOLFOXIRI + bevacizumab significantly and meaningfully improves survival of patients with metastatic colorectal cancer compared with doublets + bevacizumab and provides advantage in PFS, ORR, and R0 resection rate at the price of a moderate increase in toxicity. No increased benefit is observed among patients with BRAF-mutant tumors.”

Reference:

Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer

https://ascopubs.org/doi/full/10.1200/JCO.20.01225

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