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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., Highlights • After 3rd- or 4th-line therapy, PFS remained linear in the majority of women with metastatic triple-negative breast cancer. • The duration of each previous PFS had an impact on the OS associated with subsequent lines. • PFS2 was more strongly predictive of outcome than PFS1 for third-line therapy. • PFS2 and PFS3 had an impact on outcome irrespective of PFS1 for fourth-line therapy. • The clinical utility of nomograms including duration of each previous PFS to predict OS was not sufficient.

Background: The management of HER2+ BC has changed dramatically with the introduction and widespread use of HER2-targeted therapies, especially in the adjuvant setting. However, there is relatively limited real-world information on the impact of adjuvant Trastuzumab (aT) on patterns of recurrence and outcome of HER2+ MBC. Methods: In 2014, the 18 French Cancer Centers launched the Epidemiological Strategy and Medical Economics (ESME) program to provide real-world data on MBC patients (pts). All pts who started a 1st-line treatment for MBC between 01-Jan-2008 and 31-Dec-2014 were included. We examined clinical characteristics and outcomes (overall survival [OS] and time to next treatment [TNT]) in patients with HER2+ MBC pretreated with trastuzumab in the adjuvant setting (aT) compared with trastuzumab-naïve patients (nT) and patients with de novo HER2+ MBC (dn). Multivariate analyses adjusted for baseline demographic, prognostic factors and year of diagnosis (prior or after 2005, when aT was approved and widely administered in France for early HER2+ breast cancer). Results: Among the 15170 pts of the ESME database, 2863 (19%) were HER2+: 1093 pts (38%) had de novo and 1765 pts (62%) recurrent MBC; 63% were Hormone Receptor (HR) +; 54%, 25% and 21% had respectively 1, 2, or > 2 metastatic sites (68% visceral and 12% brain). Median time to 1st metastasis was 43.4 months (m) (95% CI: 24.6-84.4): 54 m in HR+ and 30 m in HR-. Among pts with recurrent MBC, 55% (995) had received aT. As 1st-line therapy for MBC, 90 % of pts received HER2-targeted agents (73% T-based). With a median follow-up of 46 m, median OS is 45 m (95% CI: 42.5-48). OS is significantly higher in de novo compared to recurrent MBC: 54 m (95% CI: 50.2-60.4) vs. 38.4 m (95% CI: 36.7-41.9), (p < 0.0001). Among pts with recurrent cancers, median OS is inferior in pts who had received aT, as compared to those who had not: 33.4 m (95% CI: 29.6-36.7) vs. 49.5 m (95% CI: 44.3-56.8), (p < 0.0001). Statistically significant differences persist after adjustment for age at MBC, disease-free interval, metastatic sites and RH status in the multivariate model (HR=1.45, 95% CI: 1.26-1.67) but not after adjustment for year of diagnosis (prior or after 2005) (HR=0.90, 95% CI: 0.70-1.15). Conclusions: These large-scale real-world data in patients with HER2+ MBC provide evidence that the survival outcome remain similar in patients with failure of adjuvant trastuzumab compared with trastuzumab-naïve patients after adjustment for year of diagnosis. De novo HER2+ MBC pts have the best outcomes. Data on clinical characteristics of metastasis and time to next treatment for the three subgroups will be presented at the meeting. Citation Format: Saghatchian M, Carton M, Piot I, Pérol D, Pistilli B, Brain E, Ghouadni A, Ricci F, Vanlemmens L, Loeb A, Levy C, Goncalves A, Dalenc F, Lefeuvre-Plesse C, Campone M, Jaffre A, Gourgou S, Cailliot C, Robain M, Dieras V. Impact of prior adjuvant trastuzumab (aT) on clinical characteristics, patterns of recurrence and outcome in 2863 patients with Her2 positive (HER2+) metastatic breast cancer (MBC)- Results from the French ESME UNICANCER program [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-20-03.

Background: Amongst metastatic breast cancer (MBC) patients (pts), those with triple-negative breast cancer (mTNBC) have a poor prognosis. Although chemotherapy (CT) remains the cornerstone therapy, its benefit on outcome is not established beyond second line while side effects increase and impair quality of life. Factors predicting for efficacy might help guiding in the treatment decision process. The purpose of this study was to evaluate factors predicting for progression-free survival (PFS) and overall survival (OS) in the third or fourth line treatment in pts with mTNBC within the National multicenter ESME cohort, and to build a nomogram based on the selected variables. Methods: The ESME (Epidemiological Strategy and Medical Economics) MBC database (NCT03275311) is a unique national Metastatic Breast Cancer cohort built from existing information systems, pharmacy records and patients’ electronic medical records (EMR), with homogenous on-site collected information. This prospective cohort includes all consecutive pts who initiated a first-line treatment for a MBC between 2008 and 2016 in one of the 18 French Comprehensive Cancer Centers. We searched for independent prognostic factors under third and fourth line chemotherapy (PFS3 and PFS4, OS3 and OS4) for mTNBC patients, using COX proportional hazard regression models. Variables included in the model were pts and tumour (primary cancer and MBC) characteristics, as well as observed PFS under previous lines of therapy. We built prognostic nomograms based on main prognostic factors retrieved. Nomograms’ prediction ability were evaluated by concordance index (C-index), calibration and subgroup analysis. We used a 6-month cut-off for each PFSx. Results: Among 22266 women in the ESME cohort, 2922 had a mTNBC. 1792 (61%), 1074 (37%) and 598 (20%) mTNBC pts respectively received at least 2, 3 or 4 lines of CT in the metastatic setting, with a median follow-up of 53.3 months (range 4.6-103). The median PFS3, PFS4, OS3 and OS4 were 2.3 months 95%CI [2.3-2.5], 2.1 months 95%CI [1.9-2.3], 6.6 months 95%CI [6.3-7.2] and 5.9 months 95%CI[5.2-6.4], respectively. PFS1, PFS2 and number of metastatic sites ≤3 at baseline were identified as prognostic factors by multivariate analysis both for OS3 and OS4 (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], all p Conclusion: The previous duration of each PFS is a major prognostic factor of PFS and OS in TNBC in 3rd or 4rd of CT among mTNBC pts. However, nomograms predicting for PFS and OS this setting do not reach a clinical utilityTable 1: PFS and OS according to previous PFS duration Previous PFS 1/2 (months)N=OS3 months [95%CI]HR [95%CI]pPFS3 months[95%CI]HR [95%CI]p≤6/≤65245.2 [4.7-5.9]16/≤63127.3 [6.4-8.7]0.71 [0.61; 0.82]2.4 [2.2-2.6]0.86 [0.75; 1]≤6/>611211.3 [8.1-13.4]0.48 [0.38; 0.6]2.7 [2.3-3.5]0.69 [0.56; 0.85]>6/>612611.9 [9.9-15.2]0.43 [0.34; 0.54]3.5 [3.2-4.1]0.52 [0.42; 0.64]Previous PFS1/2/3N=OS4 months [95%CI]HR [95%CI]PFS4 months [95%CI]HRp≤6/≤6 /≤62284.5 [3.9-5.4]16357.0 [4.1-10.9]0.7 [0.47; 1.04]2.1 [1.8-2.8]0.83 [0.57; 1.2]>6/≤6 />6176.9 [4.3-NA]0.7 [0.4; 1.22]3.0 [1.6-NA]0.54 [0.31; 0.94]>6/≤6 /≤61665.6 [4.7-6.7]0.65 [0.52; 0.8]2.3 [1.9-2.7]0.66 [0.54; 0.81]>6/>6 /≤6567.8 [4.9-11.1]0.54 [0.38; 0.75]2.1 [1.8-2.4]0.87 [0.64; 1.18]≤6/>6 /≤6608.1 [6.7-12.7]0.45 [0.33; 0.63]2.4 [1.9-3.0]0.65 [0.49; 0.88]≤6/>6 />61316.7 [5.9-NA]0.3 [0.16; 0.57]4.2 [2.3-NA]0.32 [0.17; 0.59]>6/>6 />62310.7 [8.5-NA]0.25 [0.14; 0.45]4.8 [3.4-8.0]0.33 [0.21; 0.51] Citation Format: Luc Cabel, Matthieu Carton, Barbare Pistilli, Florence Dalenc, Laurence Vanlemnens, Christelle Levy, William Jacot, Marc Debled, Agnes Loeb, Bruno Coudert, Thubault De la Motte Rouge, Lilian Laborde, Carine Laurent, Emmanuel Chamorey, Damien Parent, Thierry Petit, Marie-Ange Mouret-Reynier, Geneviève Perrocheau, Claire Labreveux, Thomas Bachelot, Mathieu Robain, Florence Lerebours. Prediction of PFS and OS under third and fourth line chemotherapy among metastatic triple-negative breast cancer patients in the national multicenter ESME metastatic breast cancer cohort [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-18.

PurposeThe currently ongoing Epidemiological Strategy and Medical Economics (ESME) research programme aims at centralising real-life data on oncology care for epidemiological research purposes. We draw on results from the metastatic breast cancer (MBC) cohort to illustrate the methodology used for data collection in the ESME research programme.ParticipantsAll consecutive ≥18 years patients with MBC treatment initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres were selected. Diagnostic, therapeutic and follow-up data (demographics, primary tumour, metastatic disease, treatment patterns and vital status) were collected through the course of the disease. Data collection is updated annually.Finding to dateWith a recruitment target of 30 000 patients with MBC by 2019, we currently screened a total of 45 329 patients, and >16 700 patients with a metastatic disease treatment initiated after 2008 have been selected. 20.7% of patients had an hormone receptor (HR)-negative MBC, 73.7% had a HER2-negative MBC and 13.9% were classified as triple-negative BC (ie, HER2 and HR status both negative). Median follow-up duration from MBC diagnosis was 48.55 months for the whole cohort.Future plansThese real-world data will help standardise the management of MBC and improve patient care. A dozen of ancillary research projects have been conducted and some of them are already accepted for publication or ready to be issued. The ESME research programme is expanding to ovarian cancer and advanced/metastatic lung cancer. Our ultimate goal is to achieve a continuous link to the data of the cohort to the French national Health Data System for centralising data on healthcare reimbursement (drugs, medical procedures), inpatient/outpatient stays and visits in primary/secondary care settings.Trial registration numberNCT03275311; Pre-results.