{Reference Type}: Clinical Trial, Phase II
{Title}: Cetuximab and vemurafenib plus FOLFIRI (5-fluorouracil/leucovorin/irinotecan) for BRAF V600E-mutated advanced colorectal cancer (IMPROVEMENT): An open-label, single-arm, phase II trial.
{Author}: Wang Z;Qin BD;Ye CY;Wang MM;Yuan LY;Dai WP;Sun L;Liu K;Qin WX;Jiao XD;Li XN;Zang YS;
{Journal}: Eur J Cancer
{Volume}: 163
{Issue}: 0
{Year}: 03 2022
{Factor}: 10.002
{DOI}: 10.1016/j.ejca.2021.12.028
{Abstract}: Current therapeutic regimens for patients with v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E-mutated colorectal cancer show unsatisfactory efficacy. To improve outcomes in this area, we assessed the safety and efficacy of a new protocol using vemurafenib and cetuximab combined with FOLFIRI (5-fluorouracil/leucovorin/irinotecan) in patients with BRAF V600E-mutated colorectal cancer.<BR>This was an investigator-initiated, open-label, single-arm, phase II trial conducted in patients with BRAF V600E-mutated advanced colorectal cancer. Patients were eligible to receive FOLFIRI combined with vemurafenib and cetuximab. The primary end-point was the objective response rate, and the secondary end-points included disease control rate, progression-free survival, overall survival and safety. This trial is registered with ClinicalTrials.gov, NCT03727763.<BR>Between 12th January 2018, and 18th June 2021, we screened 27 patients, 21 of which were enrolled in this study. Efficacy analysis showed that objective response rates were 81.0% (17/21; 95% confidence interval [CI] 57.4-93.7) in the intention-to-treat population and 85.0% (17/20, 95%CI 61.0-96.0) in the per-protocol population; two patients achieved complete response, and 15 patients achieved a partial response. In the entire cohort, the median progression-free survival was 9.7 months (95%CI 6.3-10.9), and the median overall survival for all patients was 15.4 months (95%CI 8.5-15.4). The most common adverse events (grade 3 to 4) were neutropenia (8/21), anaemia (3/21) and skin rash (3/21).<BR>Vemurafenib and cetuximab can be safely combined with the FOLFIRI regimen, showing promising antitumour activity and tolerable toxicity in patients with BRAF V600E-mutated advanced colorectal cancer. This regimen warrants a further randomised study in phase III clinical trials.