P2423 - Current Status Treatment to BRAF V600E-Mutant Metastatic Colorectal Cancer and Problems of Late Line

Hirofumi Fukushima, PhD¹, Takahito Awatsu, PhD², Shunsuke Adachi, MD¹, Takashi Murakami, PhD¹, Hiroya Ueyama, PhD¹, Dai Ishikawa, PhD¹, Tomoyoshi Shibuya, PhD¹, Mariko Hojo, PhD¹, Akihito Nagahara, PhD¹
1Department of Gastroenterology, Juntendo University Faculty of Medicine, Bunkyo-ku, Tokyo, Japan; 2Department of Gastroenterology, Juntendo University Faculty of Medicine, Bunkyo-ku Hongo, Tokyo, Japan

Introduction: BRAFV600E metastatic colorectal cancer (CRC) is an aggressive tumor with an approximate 8-10% incidence. Bad prognosis leading to a poor response to standard chemotherapy and short overall survival. In these patients, standard chemotherapy has limited efficacy, and the recent development of novel-targeted treatment regimens may significantly improve clinical outcome. The phase III BEACON trial made significant progress in the development of BRAF inhibitors by establishing binimetinib encorafenib-cetuximab as the new standard of care for patients with mCRC. Nonetheless, not all respond to this, and some responses are short-lived. The transition to the late line is particularly problematic. We retrospectively evaluated BRAFV600E metastatic CRC.

Methods:

Between April 2020 and March2024, among cases diagnosed with CRC, 172 cases in which BRAFV600E was measured were studied, the clinical characteristics and current status, and problems were discussed. BRAF-negative case from the same period was used as a control group.

Results: BRAF V600E mutant case was positive in 12 cases (6.9%). 9 cases received binimetinib encorafenib-cetuximab therapy. The average age was 59 (range 41-76: control group - 64.3) years. Three cases were male. All cases were second-line, with the number of cycles continuing ranging from 2 to 32, In the few analyses of the 9 cases, the median OS, 11.2 months (control group 13.2) and median PFS, 6.5 months (control group 7.3). No correlation with the duration of first-line treatment. Adverse events of Grade 3 or higher were not observed. 6 cases tried to 3rd line but dropped out within three months (control group median 4.2 months p >0.05 ). The overall prognosis was poorer than in the control group. Furthermore, no significant differences by age or sex, but cases of peritoneal dissemination and bone metastases had a poor prognosis.

Discussion:

BRAFV600E mutations are associated with decreased overall survival, poor treatment responses. However, because good therapeutic effects were observed in some cases, it was thought that administration at an earlier stage before peritoneal dissemination occurred would be effective.The optimal sequencing of treatment regimens for patients with BRAFV600E metastatic CRCs is an important area for future research.

Disclosures:


Hirofumi Fukushima, PhD¹, Takahito Awatsu, PhD², Shunsuke Adachi, MD¹, Takashi Murakami, PhD¹, Hiroya Ueyama, PhD¹, Dai Ishikawa, PhD¹, Tomoyoshi Shibuya, PhD¹, Mariko Hojo, PhD¹, Akihito Nagahara, PhD¹. P2423 - Current Status Treatment to BRAF V600E-Mutant Metastatic Colorectal Cancer and Problems of Late Line, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.