Bevacizumab mitigates codon specific effects of trifluridine/tipiracil on efficacy outcome parameters in metastatic colorectal cancer

• Published in: ESMO open 2023-12, Vol.8 (6), p.102064-102064, Article 102064
• Main Authors: Doleschal, Bernhard, Taghizadeh, Hossein, Lentner, Theresa, Riedl, Jakob M., Granitzer, Janine, Morariu, Darius, Decker, Jörn, Aichberger, Karl J., Webersinke, Gerald, Kirchweger, Patrick, Petzer, Andreas, Rumpold, Holger
• Format: Article
• Language: English
• Subjects: Bevacizumab; Bevacizumab - pharmacology; Bevacizumab - therapeutic use; Colonic Neoplasms; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Frontotemporal Dementia; FTD/TPI; Humans; KRAS G12; mCRC; Original Research; Proto-Oncogene Proteins p21(ras) - genetics; real world data; Retrospective Studies; Trifluridine - pharmacology; Trifluridine - therapeutic use; Uracil
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2023.102064

Molecular informed therapy changed treatment patterns of metastatic colorectal cancer. Recently KRAS G12, the most prevalent RAS mutation in mCRC, was investigated to be a negative-predictive marker for efficacy of FTD/TPI. Whether this proposed selectivity remains when FTD/TPI is combined with Bevacizumab remains elusive. We aimed to describe the efficacy of FTD/TPI + Bevacizumab depending on the RAS-mutational status in a real-world population. Patients of 5 different cancer centers in Austria who received FTD/TPI + Bevacizumab in any treatment line having available information on their molecular profile were eligible. Data were retrospectively collected by chart-review. Survival data was compared by log rank test. Multivariate Cox regression models included several established co-variates. 123 patients with metastatic colorectal cancer were included in this study. Median overall survival (OS) was highly similar in the RAS WT 9.63 months (95%CI 8.055-13.775) and the RAS MT cohort 8.78 months (95%CI 8.055-11.014), which was confirmed in multivariable model adjusting for potential confounders; HR: 1.05 (95%CI 0.618-1.785; P=0.857. In addition, no effect of KRAS G12 status on patient outcome was observed. In detail, OS was 8.88 months (95%CI 7.332-12.921) in patients with KRAS G12 mutation, compared to 9.47 months (95%CI 8.088-11.375) in patients with RAS WT/no KRAS G12 disease HR 0.822 (95%CI 0.527-1.282; P=0.387). This real-world study indicates that the efficacy of FTD/TPI + Bevacizumab is independent of RAS mutational status and that Bevacizumab may therefore mitigate the potentially limited efficacy of FTD/TPI monotherapy in the KRAS G12 mutated population. •Efficacy of FTD/TPI and Bevacizumab was confirmed in largest European real world cohort•The combination of FTD/TPI and Bevacizumab showed therapeutic benefits irrespective of RAS mutational status.•KRAS G12 mutations were not significantly associated with poorer survival benefit