Pathologic complete response after first-line tislelizumab, cetuximab, and dabrafenib in microsatellite-stable BRAF V600E-mutant metastatic colorectal cancer: a case report.

Abstract

BRAF V600E-mutant metastatic colorectal cancer (mCRC) is characterized by aggressive disease behavior and limited responsiveness to conventional systemic therapy. Although BRAF/EGFR-targeted therapies have improved clinical outcomes, durable complete remission remains uncommon, particularly in microsatellite-stable (MSS) disease. We report the case of a 26-year-old woman with MSS, BRAF V600E-mutant sigmoid colon adenocarcinoma and synchronous liver and omental metastases (cT4aN2M1c, stage IVC). Pretreatment biopsy demonstrated high programmed death-ligand 1 (PD-L1) expression (combined positive score = 20) and a high density of intratumoral CD8+ T cells (350 cells/mm2). Because the patient declined cytotoxic chemotherapy, first-line treatment consisted of tislelizumab combined with cetuximab and dabrafenib. After approximately 4 months of systemic therapy, radiological assessment showed a partial response, accompanied by normalization of serum marker levels, enabling conversion surgery. Histopathological examination confirmed a pathological complete response in the primary tumor and all resected metastatic lesions. A personalized tumor-informed circulating tumor DNA assay performed 3 months after surgery was negative. At the latest follow-up (35 months after treatment initiation), the patient remained free of clinical and radiological evidence of disease recurrence. This case highlights the possibility that selected patients with MSS, BRAF V600E-mutant mCRC may achieve durable remission with combined programmed cell death protein 1 blockade and dual-targeted therapy. The observed association between high intratumoral CD8+ T-cell infiltration, elevated PD-L1 expression, and favorable treatment response should be considered hypothesis-generating and requires validation in prospective biomarker-driven studies.