Incidence and prognostic factors in patents (pts) with mutant BRAF (mBRAF) metastatic colorectal cancer (mCRC) in Russia.

Abstract

e15035 Background: m BRAF mCRC has the aggressive phenotype. The incidence of such mutation in Europe and the USA is around 8-14%, in Asian countries - 4-8%. The purpose of this population-based study was to determine the incidence and identifying prognostic factors in pts with mBRAF mCRC in Russia. Methods: A multicenter retrospective analysis of clinical data and treatment results of pts with mBRAF mCRC was performed. The main method for determining mutations was a PCR. The main efficacy endpoint was progression free survival (PFS) at the 1st line. Multivariate analysis was performed using Cox regression model. Results: 437 out of 8646 pts (5%) with a known mutational status had m BRAF (V600E). Clinical data were collected from 119/437 (27.2%): female - 65.5%, average age - 60 years (28-86), MSI-H -10%; the right-sided primary tumor – in 65%, left-sided – in 17%, rectum – in 18%; the primary tumor was removed in 76%; adjuvant chemotherapy was administered in 30%; lung metastases – in 15 %, liver - 45%, peritoneal metastases – in 38%; metastasectomy was performed in 13% pts. The first line was administered in 86 (72%) pts: FOLFIRI / XELIRI - 17 (20%), FOLFOX / XELOX - 50 (58%), FOLFOXIRI - 12 (14%), monotherapy of fluoropyrimidines – in 7 (8%). Bevacizumab was added to chemotherapy at 1st line in 25 (29%) patients, anti-EGFR – in 8 (9%) pts. PFS at the 1st line was 7 months: XELOX / FOLFOX - 7, FOLFOXIRI - 7, FOLFIRI / XELIRI - 6 and fluoropyrimidines - 2 months (HR 0.9, 95% CI 0.6-1.1, p = 0.3). None of the clinical or morphological factors except the presence of metastases in the retroperitoneal lymph nodes (HR 2.6, 95% CI 1.3-5.4, p = 0.006) did not have an independent negative prognostic value. Conclusions: In contrast to Western countries the incidence of mBRAF gene in the population of pts with mCRC in the Russia is low and we found a high incidence of localization of the primary tumor in the rectum. We didn’t reveal any prognostic factors except metastases in the retroperitoneal lymph nodes, and didn’t reveal any differences between the usual duplets and standard regimen for such mutation - FOLFOXIRI in term of 1st line PFS. This suggests we need a prospective randomized study to determine the optimal regimen of chemotherapy at 1st line for mBRAF mCRC pts.