Real-world first-line treatment of patients with BRAFV600E-mutant metastatic colorectal cancer: the CAPSTAN CRC study

• Published in: ESMO open 2022-12, Vol.7 (6), p.100603-100603, Article 100603
• Main Authors: Martinelli, E., Cremolini, C., Mazard, T., Vidal, J., Virchow, I., Tougeron, D., Cuyle, P.-J., Chibaudel, B., Kim, S., Ghanem, I., Asselain, B., Castagné, C., Zkik, A., Khan, S., Arnold, D.
• Format: Article
• Language: English
• Subjects: BRAF mutation; metastatic colorectal cancer; observational; Original Research; real world; targeted therapy; treatment practices
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2022.100603

BRAFV600E mutations occur in 8%-12% of metastatic colorectal cancer (mCRC) cases and are associated with poor survival. European guidelines recommend combination (doublet or triplet) chemotherapy plus bevacizumab in first line. However, an unmet need remains for more effective treatments for these patients. CAPSTAN CRC is a European, retrospective, multicenter, observational study evaluating real-world treatment practices for patients with BRAFV600E-mutant mCRC treated between 1 January 2016 and 31 January 2020. The primary objective was to describe first-line treatment patterns. Secondary objectives included describing baseline demographics, mutational testing procedures, treatment effectiveness, and safety. In total, 255 patients (median age 66.0 years; 58.4% female) with BRAFV600E-mutant unresectable mCRC from seven countries were included. Most had right-sided tumors (52.5%) and presented with synchronous disease at diagnosis (66.4%). Chemotherapy plus targeted therapy (68.7%) was preferred at first line over chemotherapy alone (31.3%). The main first-line treatments were FOLFOX plus bevacizumab (27.1%) and FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, irinotecan) with/without bevacizumab (27.1%/19.2%). Median duration of first-line treatment was 4.9 months. Overall, 52.5% received second-line treatment. Across all first-line regimens, progression-free survival (PFS) and overall survival were 6.0 [95% confidence interval (CI) 5.3-6.7] months and 12.9 (95% CI 11.6-14.1) months, respectively. Triplet plus targeted therapy was associated with more adverse events (75.0%) compared with triplet chemotherapy alone (50.0%) and doublet chemotherapy alone (36.1%). Multivariate analysis identified low body mass index and presence of three or more metastatic sites as significant prognostic factors for PFS. This study is, to date, the largest real-world analysis of patients with BRAFV600E-mutant mCRC, providing valuable insights into routine first-line treatment practices for these patients. The data highlight the intrinsic aggressiveness of this disease subgroup, confirming results from previous real-world studies and clinical trials, and stressing the urgent need for more effective treatment options in this setting. •Most patients with BRAF-mutant mCRC received doublet chemotherapy with or without targeted therapy at first line.•The triplet chemotherapy + targeted therapy group had the highest ORR (52.5%) versus the other treatment groups.•Median PFS was