МЕТААНАЛИЗ ИССЛЕДОВАНИЙ ПО СРАВНЕНИЮ ЭФФЕКТИВНОСТИ РЕЖИМОВ FOLFOXIRI И FOLFOX ИЛИ FOLFIRI С ТАРГЕТНОЙ ТЕРАПИЕЙ ПРИ МЕТАСТАТИЧЕСКОМ РАКЕ ТОЛСТОЙ КИШКИ С МУТАЦИЕЙ В ГЕНЕ BRAF

Introduction. Based on the subgroup analysis of the TRIBE study FOLFOXIRI with bevacizumab is the recommended option for patients (pts) with m BRAF metastatic colorectal cancer (mCRC) in the 1st line. However, subgroup analysis of other studies showed conflicting results. Therefore, we performed systemic review and meta-analysis to compare efficacy FOLFOXIRI and doublets with targeted therapy in pts with m BRAF mCRC in terms of progression free survival (PFS), objective response rate (ORR) and overall survival (OS). Methods. We performed a search of all prospective randomizes studies in PubMed, ASCO and ESMO congresses for all years before May, 2020, compared FOLFOXIRI plus bevacizumab or anti-EGFR antibodies and FOLFOX or FOLFIRI with targeted agents at the 1st line with information of the BR AF status. Primary outcome was hazard ratio (HR) for PFS and 95% confidence interval (CI); secondary – HR for OS and odds ratio (OD) for ORR. Fixed effects were used for analysis. Meta-analysis was conducted by Review Manager Ver. 5.3. Results. We identified 6 trials (CHARTA, STEAM, TRIBE, TRIBE2, VISNU, METHEP2), which included 158 pts with mBRAF (FOLFOXIRI – 82 (52%) and doublets – 76 (48%). According to results of the meta-analysis there was a tendency for higher ORR in pts with FOLFOXIRI (OR 2.07, 95% CI 0.61–7.06; p = 0.24; I 2  = 27%, p for heterogeneity 0.26; 3 trials). However we didn’t find any significant improvement in PFS (HR 0.89, 95% CI 0.64–1.23; p = 0.48; I 2  = 0%, p for heterogeneity 0.63; 5 trials) or OS (HR 0.9, 95% CI 0.37–1.19; p = 0.048; I 2  = 71%, p for heterogeneity 0.06; 2 trials) in the group of triplet. Conclusions. FOLFOXIRI with targeted therapy did not show significant improvement in the PFS and OS in pts with m BRAF compared with FOLFOX or FOLFIRI with targeted antibodies. A prospective randomized trial is needed to determine the optimal chemotherapy regimen at the 1 st  line for pts with m BRAF mCRC.