Entry Detail
| General information | |
| Database: | DB00016 |
| Objective: | A fluoropyrimidine plus irinotecan or oxaliplatin, combined with bevacizumab, is standard firstline treatment for metastatic colorectal cancer. Before the introduction of bevacizumab, chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) shotheyd superior efficacy as compared with fluorouracil, leucovorin, and irinotecan (FOLFIRI). In a phase 2 study, FOLFOXIRI plus bevacizumab shotheyd promising activity and an acceptable rate of adverse effects. |
| Authors: | Loupakis F, et al |
| Title: | Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. |
| Journal: | N Engl J Med. |
| Year: | 2014 |
| PMID: | 25337750 |
| Trial Design | |
| Clinical Trial Id: | NCT00719797 |
| Agent: | bevacizumab |
| Target: | Vascular endothelial growth factor Epidermal growth factor receptor |
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | FOLFOXIRI +bevacizumab |
| Study Type: | The Triplet plus Bevacizumab (TRIBE) study; a phase III, randomized, openlabel, multicenter trial conducted in III4 Italian centers |
| Key Patients Feature: | patients with unresectable metastatic colorectal cancer who had not received chemotherapy or biologic therapy for their metastatic disease but may have received adjuvant chemotherapy earlier in the disease course |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | FOLFIRI plus bevacizumab |
| Treatment Info: | randomly assigned pts to receive either FOLFIRI plus bevacizumab (control group) or FOLFOXIRI plus bevacizumab (experimental group). Up to 12 cycles of treatment were administered, followed by fluorouracil plus bevacizumab until disease progression. |
| Primary End Point: | progression free survival. Tumor assessment was centrally revietheyd. |
| Secondary End Point: | response rate, overall survival rate, resection rate of metastases, and rate of adverse events. |
| Patients Number: | 508 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | 65% in the experimental group and 53% in the control group (P=0.006) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 12.1 ms for FOLFOXIRI+bevacizumab vs 9.7 ms for FOLFIRI + bevacizumab(hazard ratio for progression, 0.75; 95% confidence interval [CI], 0.62 to 0.90; P=0.003). |
| Median OS A vs. C: | 31.0 vs. 25.8 months; hazard ratio for death, 0.79; 95% CI, 0.63 to 1.00; P=0.054 |
| Adverse Event(agent arm): | The incidences of grade 3 or 4 neurotoxicity, stomatitis, diarrhea, and neutropenia were significantly higher in the experimental group. |
| Conclusions: | FOLFOXIRI plus bevacizumab, as compared with FOLFIRI plus bevacizumab, improved the outcome in patients with metastatic colorectal cancer and increased the incidence of some adverse events. |