441P - A study of vemurafenib and cetuximab in combination with FOLFIRI for patients with BRAF V600E-mutated advanced colorectal cancer (NCT03727763): Preliminary results

Background

The prevalence of BRAF V600E in colorectal cancer （CRC） was about 10%. Despite recent therapeutic advances, BRAF V600E mutant CRC is still a challenge with a low response rate and suboptimal survival. Here we reported the safety and preliminary anti-tumor activity of vemurafenib and cetuximab in combination with FOLFIRI for BRAF V600E-mutated advanced CRC patients.

Methods

In this single-arm, single-center trial, we are currently in enrollment of patients with BRAF V600E-mutated, RAS-wild type advanced CRC. Patients received vemurafenib 960mg orally every 12 hours, cetuximab 500mg/m² in combination with FOLFIRI, consisting of irinotecan 180mg/m² 2 hour-intravenous infusion, leucovorin 400mg/m², 5-fluorouracil (5-FU) 400mg/m² intravenous injection on day 1, followed by a 46-h continuous infusion of 5-FU (2400 mg/m²). The primary objective was to measure the objective response rate (ORR). And the secondary objective included safety, progression-free survival and overall survival.

Results

18 patients were enrolled in this study and 16 patients completed at least 3 sessions of treatment for efficacy assessment. The ORR was 81.3% with 2 complete response (CR) and 11 partial response (PR). The disease control rate (CR+PR+SD) was 100%. Out of 7 patients receiving the treatment at second or third line, 5 patients (1 CR, 4 PR) had an objective response (71.4%). 81.8% of the adverse events (AEs) were grade 1 or 2. Grade 3/4 AEs (≥2 patients) included neutropenia (8 pts, 44.4%), rash (3 pts, 16.7%), anemia (3 pts, 16.7%), fatigue (2 pts, 11.11%), diarrhea (2 pts, 11.11%), and leukopenia (2 pts, 11.11%),. 12 out of 18 patients (66.7%) reduced vemurafenib dose due to AEs, in which 4 patients reduced once from 960mg to 720mg and the remaining 8 patients reduced twice from 720mg to 480mg. Only one patient dropped out due to the intestinal obstruction.

Conclusions

A combination of vemurafenib, cetuximab and FOLFIRI was generally well-tolerated and the preliminary result indicated considerably increased response rate for advanced colorectal cancer patients with BRAF V600E mutation. The enrollment for the trial is still under way.

Clinical trial identification

NCT03727763.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.