BRAF V600E-mutant metastatic colorectal cancer (CRC) was associated with poor clinical outcomes in patients receiving systemic therapy in a real-world setting, as shown in findings from a retrospective observational study presented at the 2025 ASCO Gastrointestinal Cancer Symposium.
With a median follow-up of 43 months, 28 (57%) patients received chemotherapy, which included 14 with synchronous tumor locations and 14 with metachronous tumor locations. Data showed a median time to treatment change (TTC) of 11.5 months for frontline therapy.
Investigators reported a median overall survival (OS) of 17 months across the overall population, 15 months for patients with synchronous tumors and 18 months for those with metachronous tumors. Based on univariate analysis, factors that correlated with OS outcomes included metastasectomy, signet ring cell histology, ECOG performance status, distant lymph node metastases, peritoneal metastases and Charlston Comorbidity Index.
Glossary:
Synchronous metastases: the presence of secondary tumors (metastases) that are detected at the same time as the primary cancer.
Median time to treatment change: the average time it takes for patients to switch from one treatment to another.
Overall survival: the time from diagnosis or the start of treatment when a patient with cancer is still alive.
Metachronous tumors: new primary cancers that develop in a patient who already had a previous, different cancer.
Metastasectomy: a surgical procedure to remove one or more metastatic tumors.
ECOG performance status of 2: a score indicating a specific level of functional impairment in a patient. With a score of 2, patients are ambulatory and capable of all self-care but unable to carry out any work activities.
Factors that correlated with OS per multivariate analysis included having a metastasectomy and an ECOG performance status of 2.
“Real-world data confirm that patients with BRAF-V600E mutant [metastatic] CRC have poor clinical outcomes,” Arwa Ahmed, of the Division of Medical Oncology in the Department of Medicine at the University of Ottawa, wrote with study coauthors. “Our analysis suggests that synchronous metastatic status did not seem to impact survival of [patients with] BRAF-V600E mutant [metastatic] CRC with resected primary tumor. Future analysis will assess the impact of mismatch repair [MMR] and microsatellite instability [MSI] on these findings.”
According to the study authors, approximately 20% of patients with CRC present with metastatic disease requiring management with systemic therapy, and the median OS of patients who receive systemic treatment exceeds 30 months. Additionally, because BRAF V600E-mutant disease confers a worse prognosis, investigators aimed to assess if metastatic status synchronous tumors or metachronous tumors could predict survival in patients with resected BRAF V600E-mutated metastatic CRC before the time in which BRAF and EGFR inhibitors became more prominent in the field.
Investigators of this retrospective observational study assessed adult patients with advanced BRAF V600E-mutant metastatic CRC who underwent treatment prior to March 31, 2021. The main end points were OS and TTC, which served as a surrogate for progression-free survival.
Data collection involved the use of electronic medical records, with investigators analyzing information.
Overall, investigators identified 71 patients with BRAF V600E-mutant metastatic CRC. Of these patients, 49 had their primary tumors resected.
Reference:
Impact of synchronous vs metachronous primary tumor resection on prognosis of BRAF-V600E mutant metastatic colorectal cancer (mCRC). Arwa Ahmed, et al. J Clin Oncol.
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