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Clinical Studies

Outcomes of patients with HER2-negative metastatic breast cancer after platinum- and non-platinum-based first-line chemotherapy among patients with and without pathogenic germline BRCA1/2 mutations

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.

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Fig. 1
Fig. 2: Progression-free survival (PFS) and overall survival (OS) in function of the chemotherapy regimen (PtCT and non-PtCT) in the gBRCA1/2m population, and in function of the tumour subtype (TNBC and HR+/HER2−).
Fig. 3: Progression-free survival (PFS) and overall survival (OS) in function of the chemotherapy regimen (PtCT and non-PtCT) in the gBRCA1/2wt population, and in function of the tumour subtype (TNBC and HR+/HER2−).

Data availability

The data presented in this study are available on reasonable request from the corresponding author.

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Acknowledgements

We thank the 18 French Comprehensive Cancer Centers (Institut Curie, Paris and Saint-Cloud; Gustave Roussy, Villejuif; Institut Cancerologie de l’Ouest, Angers and Nantes; Centre Francois Baclesse, Caen; Institut du Cancer de Montpellier, Montpellier; Centre Leon Berard, Lyon; Centre Georges-Francois Leclerc, Dijon; Centre Henri Becquerel, Rouen; Institut Claudius Regaud, Toulouse; Centre Antoine Lacassagne, Nice; Institut de Cancerologie de Lorraine, Nancy; Centre Eugene Marquis, Rennes; Institut Paoli-Calmettes, Marseille; Centre Jean Perrin, Clermont Ferrand; Institut Bergonie, Bordeaux; Centre Paul Strauss, Strasbourg; Institut de Cancerologie Jean-Godinot, Reims; and Centre Oscar Lambret, Lille) for providing the data and each ESME contact for coordinating the project at the local level. Moreover, we thank the central coordination team of Unicancer and the ESME strategic and scientific committee members for their ongoing support.

Funding

The ESME-MBC database receives financial support from an industrial consortium (Roche, Pfizer, AstraZeneca, MSD, Eisai, and Daiichi Sankyo). Data collection, analysis and publication are managed entirely by UNICANCER, independently of the industrial consortium.

Author information

Authors and Affiliations

Authors

Contributions

WJ: conceptualisation, formal analysis, investigation, methodology, visualisation, writing—original draft, writing—review and editing. AL: conceptualisation, data curation, formal analysis, methodology, visualisation, funding acquisition, writing—original draft, writing—review and editing. CV: investigation, writing—review and editing. AM: investigation, writing—review and editing. TDLMR: investigation, writing—review and editing. LC: investigation, writing—review and editing. CL: investigation, writing—review and editing. AP: investigation, writing—review and editing. ID: investigation, writing—review and editing. LU: investigation, writing—review and editing. JCT: investigation, writing—review and editing. MR: investigation, writing—review and editing. OC: investigation, writing—review and editing. OT: investigation, writing—review and editing. TF: conceptualisation, data curation, investigation, writing—review and editing. JSF: conceptualisation, investigation, writing—review and editing. SD: conceptualisation, investigation, writing—review and editing.

Corresponding author

Correspondence to William Jacot.

Ethics declarations

Ethics approval and consent to participate

This study was authorised by the French data protection authority ([Registration ID 1704113 and authorisation N_DE-2013.-117], NCT03275311). Moreover, in compliance with the applicable European regulations, a complementary authorisation was obtained for the ESME Data Warehouse on 14 October 2019. All data were obtained retrospectively, and no procedure was taken to recover unavailable data by contacting healthcare providers or patients. The present analysis was approved by an independent French ethics committee (Comité de Protection des Personnes Sud-Est II-2015–79).

Consent to publish

Not applicable.

Competing interests

Dr. TDlMR reports personal fees and non-financial support from AstraZeneca, personal fees from Clovis oncology, personal fees from GSK, grant and personal fees from MSD, grant, personal fees and non-financial support from Pfizer, personal fees from Tesaro, personal fees and non-financial support from Roche Genentech, grant from SeattleGenetics, grant from Novartis, personal fees from Eisai, grant from Novartis, outside the submitted work. Dr. SD reports grants and non-financial support from Pfizer, grants from Novartis, grants and non-financial support from AstraZeneca, grants and non-financial support from Roche Genentech, grants from Lilly, grants from Puma, grants from Myriad, grants from Orion, grants from Amgen, grants from Sanofi, grants from Genomic Health, grants from GE, grants from Servier, grants from MSD, grants from BMS, grants from Pierre Fabre, grants from Seagen, grants from Exact Sciences, grants from Rappta, grants from Besins, grants from European Commission, grants from French government grants, grants from Fondation ARC, outside the submitted work. Dr. TF reports fees to its institution from Cellectis, grants from BMS, outside the submitted work. Dr. JSF reports personal fees from Roche Genentech, personal fees and non-financial support from SeattleGenetics, personal fees and non-financial support from Novartis, personal fees and non-financial support from Pfizer, personal fees and non-financial support from Lilly, personal fees and non-financial support from Novartis, personal fees and non-financial support from GSK, personal fees and non-financial support from Clovis oncoloy, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Daiichi Sankyo, personal fees and non-financial support from Gilead, personal fees and non-financial support from MSD, personal fees and non-financial support from Pierre Fabre, personal fees and non-financial support from Amgen, outside the submitted work. Dr. WJ reports grants, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Eisai, personal fees and non-financial support from Novartis, personal fees and non-financial support from Roche, personal fees and non-financial support from Pfizer, personal fees and non-financial support from Eli Lilly, personal fees from MSD, personal fees from BMS, personal fees and non-financial support from Chugai, personal fees from Seagen, grants and personal fees from Daiichi Sankyo, outside the submitted work. Dr. CL reports personal fees from Roche, non-financial support from MSD, grants from Lilly, other from DAIICHI, other from Pfizer, other from SANDOZ, outside the submitted work. Dr. AP reports other from Lilly, other from Pfizer, other from Pierre Fabre, others from Daiichi Sankyo, outside the submitted work. Dr. MR reports non-financial support from Roche, outside of the submitted work. Dr. JCT reports personal fees and non-financial support from PFIZER, personal fees from MSD, personal fees from ASTRA ZENECA, non-financial support from NOVARTIS, outside the submitted work. Dr. OT reports grants and personal fees from Roche, grants and personal fees from MSD-Merck, grants from BMS, personal fees from Novartis-Sandoz, personal fees from Pfizer, personal fees from Lilly, personal fees from AstraZeneca, personal fees from Daiichi Sankyo, personal fees from Eisai, personal fees from Pierre Fabre, personal fees from Seagen, personal fees from Gilead, outside the submitted work. Dr. CV reports personal fees from AstraZeneca, grants from BMS, non-financial support from IPSEN, personal fees from Novartis, personal fees and non-financial support from Pfizer, personal fees from Daiichi Sankyo, outside the submitted work. Drs. LC, OC, ID, AL, AM and LU have nothing to disclose.

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Jacot, W., Lusque, A., Vicier, C. et al. Outcomes of patients with HER2-negative metastatic breast cancer after platinum- and non-platinum-based first-line chemotherapy among patients with and without pathogenic germline BRCA1/2 mutations. Br J Cancer 127, 1963–1973 (2022). https://doi.org/10.1038/s41416-022-02003-1

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