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. 2021 Apr:56:18-25.
doi: 10.1016/j.breast.2021.01.006. Epub 2021 Jan 30.

Outcome beyond third-line chemotherapy for metastatic triple-negative breast cancer in the French ESME program

Luc Cabel  1 , Matthieu Carton  2 , Barbara Pistilli  3 , Florence Dalenc  4 , Laurence Vanlemnens  5 , Christelle Levy  6 , William Jacot  7 , Michel Debled  8 , Agnes Loeb  9 , Audrey Hennequin  10 , Thibault De la Motte Rouge  11 , Lilian Laborde  12 , Carine Laurent  13 , E Chamorey  14 , Damien Parent  15 , Thierry Petit  16 , Marie-Ange Mouret-Reynier  17 , Mario Campone  18 , Geneviève Perrocheau  18 , Claire Labreveux  19 , Thomas Bachelot  20 , Mathieu Robain  19 , Florence Lerebours  2
Affiliations

Outcome beyond third-line chemotherapy for metastatic triple-negative breast cancer in the French ESME program

Luc Cabel et al. Breast. 2021 Apr.

Abstract

Purpose: Among metastatic breast cancer (MBC) patients, those with a triple-negative breast cancer phenotype (mTNBC) have the worst prognosis, but the benefit of chemotherapy beyond second line on outcome remains uncertain. The purpose of this study was to identify predictive factors of outcome after third- or fourth-line chemotherapy.

Methods: The ESME-MBC database is a French prospective real-life cohort with homogeneous data collection, including patients who initiated first-line treatment for MBC (2008-2016) in 18 cancer centers. After selection of mTNBC cases, we searched for independent predictive factors (Cox proportional-hazards regression models) for overall survival (OS) on third- and fourth-line chemotherapy (OS3, OS4). We built prognostic nomograms based on the main prognostic factors identified.

Results: Of the 22,266 MBC cases in the ESME cohort, 2903 were mTNBC, 1074 (37%) and 598 (20%) of which had received at least 3 or 4 lines of chemotherapy. PFS after first- and second-line chemotherapy (PFS1, PFS2) and number of metastatic sites ≥3 at baseline were identified by multivariate analysis as prognostic factors for both OS3 (HR = 0.76 95%CI[0.66-0.88], HR = 0.55 95%CI[0.46-0.65], HR = 1.36 95%CI[1.14-1.62], respectively), and OS4 (HR = 0.76 95%CI[0.63-0.91], HR = 0.56 95%CI[0.45-0.7], HR = 1.37 95%CI[1.07-1.74]), respectively. In addition, metastasis-free interval was identified as a prognostic factor for OS3 (p = 0.01), while PFS3 influenced OS4 (HR = 0.75 95%CI[0.57-0.98]). Nomograms predicting OS3 and OS4 achieved a C-index of 0.62 and 0.61, respectively.

Conclusion: The duration of each previous PFS is a major prognostic factor for OS in mTNBC patients receiving third- or fourth-line chemotherapy. The clinical utility of nomograms including this information was not demonstrated.

Keywords: Chemotherapy; Heavily pretreated; Metastatic breast cancer; Prognostic factors; Real-life.

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Conflict of interest statement

Declaration of competing interest Dr. De La Motte Rouge reports personal fees and non-financial support from ASTRAZENECA, grants, personal fees and non-financial support from PFIZER, grants from NOVARTIS, personal fees and non-financial support from EISAI, personal fees and non-financial support from ROCHE, grants and non-financial support from MSD, outside the submitted work. Dr. Robain reports ESME Platform was supported by Roche, Astra Zeneca, BMS, Pfizer, Daiichi Sankyo, Eisai. Prof. Campone reports grants from Pfizer, grants from AstraZeneca, grants from Sanofi, grants from Pierre Fabre, grants from Takeda, personal fees from Novartis, personal fees from Lilly, outside the submitted work. Dr. MOURET-REYNIER reports grants from Novartis, Lilly, Pfizer, Roche, Pierre Fabre, MSD, outside the submitted work. All other authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Flow diagram of patients selected from the ESME database.
Fig. 2
Fig. 2
Progression-free survival (PFS) and overall survival (OS) for patients receiving third-line (PFS3/OS3) and fourth-line (PFS4/OS4) chemotherapy for mTNBC. PFS3 (A), OS3 (B), PFS4 (C), OS4 (D).
Fig. 3
Fig. 3
Duration of PFS on third-line (A) or fourth-line (B) chemotherapy, red: PFS < 6 months and green: PFS > 6 months. The height of each column is proportional to the number of patients of each profile.
Fig. 4
Fig. 4
OS according to previous PFS duration (< 6 or ≥ 6 months). OS3 (A). OS4 (B).
See this image and copyright information in PMC

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