Entry Detail
| General information | |
| Database: | DB00037 |
| Objective: | BRAF V600E mutation plays a negative prognostic role in metastatic colorectal cancer (mCRC), leading to a median Progression Free Survival (PFS) of 46months with firstline conventional treatments. Their group recently reported in a retrospective exploratory analysis of a phase II trial that FOLFOXIRI (5FU/LV+Oxaliplatin+Irinotecan) plus bevacizumab might allow to achieve remarkable results in terms of PFS and Overall Survival (OS) also in this poorprognosis subgroup. The aim of this work was to prospectively validate our retrospective finding. |
| Authors: | Loupakis F, et al |
| Title: | FOLFOXIRI plus bevacizumab as firstline treatment in BRAF mutant metastatic colorectal cancer. |
| Journal: | Eur J Cancer. |
| Year: | 2014 |
| PMID: | 24138831 |
| Trial Design | |
| Clinical Trial Id: | NCT01437618 |
| 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: | a phase II trial |
| Key Patients Feature: | histological diagnosis of colorectal adenocarcinoma; metastatic disease deemed initially unresectable; age 18-75 years; ECOG PS of 0-2 if patients were aged (70 years, or 0 if they were aged 71-75 years); measurable disease according to Response Evaluation Criteria In Solid Tumours (RECIST 1.0), adequate haematological, liver, and renal function; previous adjuvant oxaliplatinbased chemotherapy allowed if concluded more than 12 months before relapse. |
| Biomarker: | BRAF mutant |
| Biomark Analysis: | as in the conclusion |
| Control Group Info: | single arm |
| Treatment Info: | The trial was designed to detect an increase in 6monthProgression Free Rate (6mPFR) from 45% to 80% in a population of BRAF mutant mCRC patients treated with firstline FOLFOXIRI plus bevacizumab. Secondary endpoints were PFS, OS, response rate (RR) and the analysis of outcome parameters in the pooled population consisting of both retrospectively and prospectively included patients. |
| Primary End Point: | Primary end point was to detect an increase in 6 monthProgression Free Rate (6 mPFR) from 45% to 80% in a population of BRAF mutant mCRC patients treated with firstline FOLFOXIRI plus bevacizumab. |
| Secondary End Point: | Secondary endpoints were PFS, OS, response rate (RR) and the analysis of outcome parameters in the pooled population consisting of both retrospectively and prospectively included patients. |
| Patients Number: | 214 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | In the pooled population: Overall RR was 72% |
| Disease Control Rate: | In the pooled population: 88% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | in the validation cohort: 6mPFR(6monthProgression Free Rate ) was 73%, median PFS was 9.2 months; In the pooled population: 6mPFR was 84%. Median PFS was 11.8 months. |
| Median OS A vs. C: | In the validation cohort:24.1 months;In the pooled population: 24.1 months |
| Adverse Event(agent arm): | In the validation cohort: The relative doseintensity was 92% for oxaliplatin and irinotecan and 89% for 5FU and bevacizumab. Treatment was delayed because of toxicity or adverse events in 16 (11%) cycles. The most common G34 adverse event was neutropenia, that occurred in 6 (40%) patients and was complicated by fever in one case. Other G34 adverse events were stomatitis (20%), diarrhoea (13%), asthenia (13%) and venous thrombosis (13%). |
| Conclusions: | Lacking randomised trials in this specific molecular subgroup, FOLFOXIRI plus bevacizumab might be a reasonable option for the firstline treatment of BRAF mutant mCRC patients. |