440TiP TRESBIEN (OGSG 2101): Encorafenib, binimetinib and cetuximab for early relapse stage II/III BRAF V600E-mutated CRC

Abstract

The BRAF V600E mutation accounts for approximately 5% of colorectal cancer (CRC) cases and is an extremely poor prognostic factor. There are no clear recommendations for patients with early recurrent BRAF V600E-mutated CRC, during or after adjuvant chemotherapy. Recently, triplet therapy of encorafenib, binimetinib, and cetuximab, resulted in significantly longer overall survival and a higher response rate than standard chemotherapy in patients with previously treated metastatic CRC with the BRAF V600E mutation (Kopetz S, N Engl J Med. 2019.). Furthermore, in first-line treatment for BRAF V600E-mutated CRC, triplet therapy showed a promising response rate and disease control rate (Cutsem EV, Ann Oncol. 2021). These results suggest that triplet therapy may be effective even in early recurrent BRAF V600E-mutated CRC during or after adjuvant chemotherapy. The TRESBIEN study is an open-label, multicenter, single-arm phase II study designed to evaluate whether encorafenib, binimetinib, and cetuximab are effective for patients with early recurrent BRAF V600E-mutated CRC during or after adjuvant chemotherapy (jRCTs051210152). The main inclusion criteria were BRAF V600E- mutated stage II/III colorectal adenocarcinoma after radical resection, recurrence during or within six months of adjuvant chemotherapy with measurable lesions, no prior treatment with encorafenib, binimetinib, or cetuximab, age ≥ 20 years, ECOG PS 0 to 2, with adequate organ function. Patients will receive encorafenib, binimetinib, and cetuximab. The primary endpoint was objective response rate. To achieve 90% power to show a significant response benefit with a one-sided alpha level of 0.05, assuming a threshold objective response rate of 6.0% and an expected value of at least 26.0%, we estimated that 25 patients were required. The secondary endpoints included overall survival, progression-free survival, disease control rate, duration of response, time to treatment failure, and safety. This is the first study to investigate whether triplet therapy combined with encorafenib, binimetinib, and cetuximab is effective for the treatment of early recurrent BRAF V600E-mutated CRC. The first patient was enrolled in January 2022. jRCTs051210152. Osaka Gastrointestinal cancer chemotherapy Study Group (OGSG).