1. Prognosis and chemosensitivity of non-V600E BRAF mutations in metastatic colorectal carcinoma (mCRC): An AGEO French multicenter retrospective cohort
- Author
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Jean-Marc Phelip, Emmanuelle Norguet, Nelson Lourenco, Julie Dremaux, Côme Lepage, David Tougeron, Astrid Lièvre, Jean-Baptiste Bachet, Thomas Walter, Romain Coriat, Vincent Nicolai, Anthony Turpin, Aline Derosiere, David Sefrioui, Vincent Hautefeuille, Morgane Caulet, Pascal Artru, Julien Lazartigues, Astrid Pozet, David Malka, Université de Picardie Jules Verne (UPJV), Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Service d'oncologie médicale (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre de Bioinformatique (CBIO), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Clinique Saint Jean, Sorbonne Université (SU), Service d'Hépato-gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU de Tours), Centre Hospitalier Université Laval [Quebec] (CHUL), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Inserm U1016, Paris Descartes University, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), and Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Colorectal cancer ,[SDV]Life Sciences [q-bio] ,education ,Retrospective cohort study ,medicine.disease ,digestive system diseases ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,business ,neoplasms ,V600E ,030215 immunology - Abstract
3575 Background: BRAF mutations are present in 5-15% of mCRC. V600E BRAF mutations account for ~80% of cases and are mostly found in right-sided tumors. Non-V600E BRAF mutations are rare (~2% of mCRC), mostly left-sided. Although BRAF V600E mutations are associated with a dismal prognosis, some studies suggest that non-V600E BRAF mutations may be associated with a favorable outcome. The chemosensitivity of non-V600E BRAF-mutated mCRC has never been studied. Methods: From 2017 to 2018, all consecutive patients (pts) with non-V600E BRAF-mutated mCRC (next generation sequencing) treated in the participating centers were included. Survival analyses were performed using Kaplan-Meier method and LogRank test. Results: A total of 108 pts in 34 centers in France were included between October 2017 and August 2018 (median age, 66 years [range, 58-77]; ECOG performance status 0-1, 86%). The primary was mostly left-sided (66%). Main metastatic sites were the liver (73%), lungs (33%), lymph nodes (39%) and peritoneum (26%). D594 (34%), G469 (15%), K601 (11%), N581 (7%) and L597 (7%) were the most frequent mutations. A concomitant RAS mutation was found in 22% of pts. Microsatellite instability (MSI) was found in 3/67 pts (4.5%). First-line chemotherapy (CTx) (n = 69) efficacy was (overall response rate/disease control rate) 49%/77% (anti-EGFR-containing CTx [n = 20], 75%/85%; antiangiogenic-containing CTx [n = 22], 55%/73%). Median overall survival (mOS) was 25.6 months (95% CI : 17.1-43.8) overall; it was 8.0 months with best supportive care alone (n = 10), 16.0 months with palliative CTx alone (n = 63), and attained 105.1 months with curative-intent management of metastases (n = 35). mOS did not differ according to sidedness (p = 0.22), type of mutation (p = 0.52), or its functional impact on BRAF (p = 0.19). Conclusions: Non-V600E BRAF-mutated mCRC retain sensitivity to CTx + biologics and harbor a good prognosis (especially when amenable to curative-intent surgery), regardless of the type of mutation and its impact on BRAF kinase function. Contrarily to BRAF V600E mutations, non-V600E mutations may occur along with RAS mutations, but uncommonly with MSI.
- Published
- 2019
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