Overall Survival, BRAF, RAS, and MSI Status in Patients Who Underwent Cetuximab After Refractory Chemotherapy for Metastatic Colorectal Cancer

• Published in: Journal of gastrointestinal cancer Vol. 55; no. 1; pp. 344 - 354
• Main Authors: Santos, Florinda A., Reis, Rui Manuel, Barroti, Lucas C., Pereira, Allan A. L., Matsushita, Marcus M., de Carvalho, Ana Carolina, Datorre, José Guilherme, Berardinelli, Gustavo N., Araujo, Raphael L. C.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.03.2024
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer Research; Cetuximab - therapeutic use; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Drug Resistance, Neoplasm - genetics; Female; Gastroenterology; GTP Phosphohydrolases - genetics; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Membrane Proteins - genetics; Microsatellite Instability; Middle Aged; Mutation; Oncology; Prognosis; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras) - genetics; Radiotherapy; Retrospective Studies; Chemotherapy; RAS status; Metastatic colorectal; BRAF; Microsatellite instability; Cetuximab; Epidermal growth factor receptor
• ISSN: 1941-6628; 1941-6636; 1941-6636
• DOI: 10.1007/s12029-023-00964-x

Purpose Evaluate overall survival (OS), RAS, BRAF, and MSI frequencies in patients with metastatic colorectal cancer (mCRC), refractory to chemotherapy, and finally treated with cetuximab. Methods A retrospective cohort study to evaluate 211 mCRC patients with wild-type KRAS treated with cetuximab. BRAF V600E, KRAS, NRAS gene mutations, and MSI status were identified using PCR techniques in a population of pre-treated patients who were refractory to fluoropyrimidines, oxaliplatin, and irinotecan. In addition, we evaluated the mutation frequency of the BRAF and NRAS genes and the MSI status of this population. Uni- and multivariate analyses were performed for independent prognostic factors of OS. Results The median OS was 10.4 months, 6.6 months for patients with right and 11.5 months for left colon cancers ( p  = 0.02). The frequencies of mutations were BRAF at 3.9% (median OS of 4.9 months), NRAS at 3.38% (median OS of 6.9 months), and MSI-High status at 3.3% (median OS of 4.6 months). The OS, NRAS, and MSI frequencies were similar to those found in other studies that evaluated cetuximab in poly-treated patients and were associated with lower survival rates in univariate analyses. The frequency of BRAF mutations was lower than that found in previous studies. The only variable that remained significant for OS in the multivariate model was tumour laterality, with patients with right colon cancer presenting a worse prognosis (HR = 2.81). Conclusion Although BRAF, NRAS mutations, and MSI-High status were associated with shorter OS in univariate analyses, only tumour laterality remained an independent prognostic factor in the multivariate analysis.