A validated prognostic classifier for V600EBRAF-mutated metastatic colorectal cancer: the 'BRAF BeCool' study

Fotios Loupakis, Rossana Intini, Chiara Cremolini, Armando Orlandi, Andrea Sartore-Bianchi, Filippo Pietrantonio, Nicoletta Pella, Andrea Spallanzani, Emanuela Dell'Aquila, Mario Scartozzi, Emmanuele De Luca, Lorenza Rimassa, Vincenzo Formica, Francesco Leone, Lorenzo Calvetti, Giuseppe Aprile, Lorenzo Antonuzzo, Federica Urbano, Hans Prenen, Francesca NegriSamantha Di Donato, Pasquale Buonandi, Gianluca Tomasello, Antonio Avallone, Fable Zustovich, Roberto Moretto, Carlotta Antoniotti, Lisa Salvatore, Maria Alessandra Calegari, Salvatore Siena, Federica Morano, Elena Ongaro, Stefano Cascinu, Daniele Santini, Pina Ziranu, Marta Schirripa, Federica Buggin, Alessandra Anna Prete, Ilaria Depetris, Paola Biason, Sara Lonardi, Vittorina Zagonel, Matteo Fassan, Massimo Di Maio

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Despite the well-known negative prognostic value of the V600EBRAF mutation in patients with metastatic colorectal cancer (mCRC), its outcome is quite heterogeneous, and the basis for this prognostic heterogeneity should be better defined.METHODS: Two large retrospective series of V600EBRAF-mutated mCRC from 22 institutions served as an exploratory and validation set to develop a prognostic score. The model was internally and externally validated.RESULTS: A total of 395 V600EBRAF-mutated mCRCs were included in the exploratory set. Performance status, CA19.9, lactate dehydrogenase, neutrophil/lymphocyte ratio, grading and liver, lung and nodal involvement emerged as independent prognostic factors for overall survival (OS). Two different scoring systems were built: a 'complete' score (0-16) including all significant covariates and a 'simplified' score (0-9), based only on clinicopathological covariates, and excluding laboratory values. Adopting the complete score, proportions of patients with a low (0-4), intermediate (5-8) and high (9-16) score were 44.7%, 42.6% and 12.6%, respectively. The median OS was 29.6, 15.5 (hazard ratio [HR] for intermediate vs low risk: 2.16, 95% confidence interval [CI]: 1.44-3.22, p <.001) and 6.6 months (HR for high vs low risk: 4.72, 95% CI: 2.72-8.20, p <.001). Similar results were observed also after adjusting for the type of first-line treatment and adopting the simplified score. The simplified prognostic score derived from the exploratory set was then applied to the validation set for external confirmation.CONCLUSIONS: These scoring systems are based on easy-to-collect data and defined specific subgroups with relevant differences in their life expectancy. These tools could be useful in clinical practice, would allow better stratification of patients in clinical trials and may be adopted for proper adjustments in exploratory translational analyses.
Original languageEnglish
Pages (from-to)121-130
Number of pages10
JournalEuropean Journal of Cancer
Volume118
DOIs
Publication statusPublished - Sep 2019

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Loupakis, F., Intini, R., Cremolini, C., Orlandi, A., Sartore-Bianchi, A., Pietrantonio, F., Pella, N., Spallanzani, A., Dell'Aquila, E., Scartozzi, M., De Luca, E., Rimassa, L., Formica, V., Leone, F., Calvetti, L., Aprile, G., Antonuzzo, L., Urbano, F., Prenen, H., ... Di Maio, M. (2019). A validated prognostic classifier for V600EBRAF-mutated metastatic colorectal cancer: the 'BRAF BeCool' study. European Journal of Cancer, 118, 121-130. https://doi.org/10.1016/j.ejca.2019.06.008