Vinorelbine in BRAF V600E mutated metastatic colorectal cancer: a prospective multicentre phase II clinical study.

Background: BRAF V600E mutation defines a specific colorectal cancer (CRC) subgroup with poor prognosis. Promising preclinical data showed synthetically lethal activity of mitotic spindle poisons on BRAF- mutated and BRAF -like CRC models. We designed a phase II trial to test the activity of vinorelbine in patients with BRAF V600E mutated metastatic CRC (mCRC).

Patients and methods: Patients progressed to or not deemed eligible for standard treatments received oral (60 mg/sqm) or intravenous (25 mg/sqm) vinorelbine, on days 1 and 8 every 21 days. Primary endpoint was objective response rate (ORR).

Results: Twenty patients were enrolled; 75% of them were highly pretreated. No responses were observed (0%); only one patient had a confirmed disease stabilisation (5%). Median progression-free survival was 1 month (95% CI 0.8 to 1.8), median overall survival was 2.1 months (95% CI 1.6 to 3.7). No serious adverse events were observed.

Conclusions: Despite encouraging preclinical data, our study did not show signs of clinical activity for vinorelbine in this patients' population. Further investigations on molecular heterogeneity and dynamic evolution of BRAF V600E mutated mCRC are needed.