William Jacot1, Amélie Lusque2, Cécile Vicier3, Audrey Mailliez4, Thibault de La Motte Rouge5, Luc Cabel6, Christelle Levy7, Anne Patsouris8, Isabelle Desmoulins9, Lionel Uwer10, Jean-Christophe Thery11, Mathieu Robain12, Olivier Caron13, Olivier Tredan14, Thomas Filleron2, Jean-Sébastien Frenel15, Suzette Delaloge13. 1. Institut du Cancer de Montpellier (ICM), INSERM U1194, Montpellier University, Montpellier, 34298, France. William.Jacot@icm.unicancer.fr. 2. Institut Claudius Regaud-IUCT Oncopole, Toulouse, France. 3. Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France. 4. Centre Oscar Lambret, Lille, France. 5. Centre Eugène Marquis, Rennes, France. 6. Institut Curie-UMR 144-CNRS, Paris, France. 7. Centre François Baclesse, Caen, France. 8. Institut de Cancérologie de l'Ouest, Pays de Loire, Angers, France. 9. Centre Georges François Leclerc, Dijon, France. 10. Institut de Cancérologie de Lorraine-Alexis Vautrin, Vandoeuvre-lès-Nancy, France. 11. Centre Henri Becquerel, Rouen, France. 12. UNICANCER, Paris, France. 13. Gustave Roussy, Villejuif, France. 14. Centre Léon Berard, Lyon, France. 15. Institut de Cancérologie de l'Ouest, Saint Herblain, France.
Abstract
BACKGROUND: The efficacy and added benefit of platinum-based chemotherapy (PtCT) for metastatic breast cancer (MBC) remain unclear in patients with and without germline BRCA1 or BRCA2 mutations (gBRCA1/2m and gBRCA1/2wt, respectively). METHODS: We selected from the French national real-world multicentre ESME cohort (2008-2016) all patients with HER2-negative MBC with known gBRCA1/2 status at first-line chemotherapy initiation. Using multivariable Cox models, we compared the outcome (progression-free (PFS) and overall survival (OS)) of first-line PtCT and non-PtCT regimens based on the patients' gBRCA1/2 status and tumour subtype. RESULTS: Patients who received PtCT had more aggressive tumour features. In the multivariable analysis, first-line PtCT was associated with better adjusted PFS and OS in gBRCA1/2m carriers (N = 300), compared with non-PtCT (HR 0.54, 95% CI 0.4-0.73, P < 0.001, and HR 0.70, 95% CI 0.49-0.99, P = 0.047, respectively). Conversely, outcomes were similar in gBRCA1/2wt patients (N = 922) treated with PtCT and non-PtCT, whatever the tumour subtype. Landmark analyses at months 3 and 6 post treatment initiation supported these results. CONCLUSIONS: In this pre-PARP inhibitor real-world cohort, PFS and OS were better after PtCT than non-PtCT in patients with gBRCA1/2m, but not in those with gBRCA1/2wt. These results emphasise the need of early gBRCA1/2 testing in patients with MBC. CLINICAL TRIAL NUMBER: NCT03275311.
BACKGROUND: The efficacy and added benefit of platinum-based chemotherapy (PtCT) for metastatic breast cancer (MBC) remain unclear in patients with and without germline BRCA1 or BRCA2 mutations (gBRCA1/2m and gBRCA1/2wt, respectively). METHODS: We selected from the French national real-world multicentre ESME cohort (2008-2016) all patients with HER2-negative MBC with known gBRCA1/2 status at first-line chemotherapy initiation. Using multivariable Cox models, we compared the outcome (progression-free (PFS) and overall survival (OS)) of first-line PtCT and non-PtCT regimens based on the patients' gBRCA1/2 status and tumour subtype. RESULTS: Patients who received PtCT had more aggressive tumour features. In the multivariable analysis, first-line PtCT was associated with better adjusted PFS and OS in gBRCA1/2m carriers (N = 300), compared with non-PtCT (HR 0.54, 95% CI 0.4-0.73, P < 0.001, and HR 0.70, 95% CI 0.49-0.99, P = 0.047, respectively). Conversely, outcomes were similar in gBRCA1/2wt patients (N = 922) treated with PtCT and non-PtCT, whatever the tumour subtype. Landmark analyses at months 3 and 6 post treatment initiation supported these results. CONCLUSIONS: In this pre-PARP inhibitor real-world cohort, PFS and OS were better after PtCT than non-PtCT in patients with gBRCA1/2m, but not in those with gBRCA1/2wt. These results emphasise the need of early gBRCA1/2 testing in patients with MBC. CLINICAL TRIAL NUMBER: NCT03275311.
Authors: Sam J Egger; Melina L Willson; Jenna Morgan; Harriet S Walker; Sue Carrick; Davina Ghersi; Nicholas Wilcken Journal: Cochrane Database Syst Rev Date: 2017-06-23