2143 - Clinical impact of BRAF V600E mutations in patients (pts) with resectable solitary colorectal liver metastases (CRLM)

Background

Patients (pts) who underwent a curative resection for solitary colorectal liver metastasis (CRLM) have a relatively favorable prognosis. Clinical impact of BRAF V600E mutations in those pts remains unclear.

Methods

Consecutive pts who had undergone initial hepatectomy for histologically confirmed solitary CRLM were included. Tumor RAS (KRAS/NRAS)/BRAF V600E mutation tests were centrally performed by a PCR method. The association between BRAF V600E mutation and survival outcome in pts with resectable solitary CRLM was retrospectively investigated.

Results

From Jan 2005 to Dec 2017, 218 pts were included with a median follow-up of 52 months (m). BRAF mutant (mBRAF) was observed in 5 (2.3%) pts, while mRAS was in 92 (42.2%) pts and RAS/BRAF wild-type (wRAS/BRAF) was in 121 (55.5%) pts. mBRAF was associated with a higher serum CA19-9 level at pre-hepatectomy (p = 0.03). Median longest diameter for solitary CRLM were similar among three cohorts (19 mm vs. 25 mm vs. 27 mm, p = 0.21). However, all the mBRAF pts experienced early recurrence within 9 m. In the univariate analysis, mBRAF was associated with a worse survival in terms of both recurrence-free survival (RFS) with the hazard ratio (HR) of 8.68 for mBRAF vs. wRAS/BRAF (mBRAF vs. mRAS vs. wRAS/BRAF; median, 4.8 m vs. 17.1 m vs. not reached, p < 0.001: 3-year RFS rate, 0% vs 39.6% vs 56.2%, p < 0.001) and overall survival (OS) with the HR of 20.8 for mBRAF vs. wRAS/BRAF (mBRAF vs. mRAS vs. wRAS/BRAF; median, 14.4 m vs. not reached vs. not reached, p < 0.001: 3-year OS rate, 20.0% vs 78.9% vs 94.9%, p < 0.001). In the multivariate analysis, mBRAF was strongly associated with a worse survival and had the highest HR among all the indicators in terms of both RFS (HR: 5.0, 95% CI: 1.8–13.8, p < 0.001) and OS (HR: 15.4, 95% CI: 5.2–45.5, p < 0.001).

Conclusions

Among resectable solitary CRLM pts, mBRAF was rare (2.3%). However, given that all the mBRAF pts experienced early recurrence and the striking value of HRs in the univariate and multivariate analyses on both RFS and OS, mBRAF itself may become the most relevant indicator beyond known clinicopathological indicators in pts with resectable solitary CRLM. A novel treatment strategy for these patients is warranted.

Clinical trial identification

UMIN000034557.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

The National Cancer Center Research Development Fund, Japan (Research number: 30-A-8, Principal investigator: Shinichiro Takahashi).

Disclosure

T. Yoshino: Research grant / Funding (self): Novartis Pharma K.K.; Research grant / Funding (self): MSD.K.K.; Research grant / Funding (self): Sumitomo Dainippon Pharma Co., Ltd.; Research grant / Funding (self): Chugai Pharmaceutical Co., Ltd.; Research grant / Funding (self): Sanofi K.K.; Research grant / Funding (self): Daiichi Sankyo Company, Limited; Research grant / Funding (self): PAREXEL International Inc.; Research grant / Funding (self): Ono Pharmaceutical Co., Ltd. H. Taniguchi: Research grant / Funding (self): Takeda; Research grant / Funding (self): Daiichi Sankyo; Research grant / Funding (self): Sysmex; Honoraria (self): Chugai; Honoraria (self): Taiho; Honoraria (self): Eli Lilly. All other authors have declared no conflicts of interest.