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Background: About 40% of breast cancer cases occur in women 65 years old (yo) or older and 20% in women over 75 yo. These numbers are expected to increase in the near future. Ironically, older patients remain underrepresented in clinical trials with no improvement in the past decade, although they may present different efficacy/toxicity profiles compared with younger adults. In this context, real life cohorts may bring valuable insight to identify potential barriers to recruitment of older patients with metastatic breast cancer (MBC) in clinical trials. Methods: We used the national Epidemio-Strategy and Medical Economics (ESME) MBC Data Platform, a multi-center real life database using a retrospective data collection process in 18 French Cancer Centers. Cases selected were adult patients with MBC whose first metastasis was treated between January 1st, 2008 and December 31st, 2016. We selected MBC women over 70 yo at the time of MBC diagnosis, with at least one line of systemic treatment and no other cancer in the 5 years before MBC. The primary objective was to describe factors associated with enrollment in clinical trials in older patients, using a multivariable Cox model. Factors included in this model were age (continuous, and by class), period (2008-2011 vs 2012-2016), phenotype (ER+, HER2+, or ER- HER2-), ECOG Performance Status (PS), treatment, metastatic sites (brain, visceral, nodes/bone only) and number, and volume of hospital activity. No geriatric description could be extracted from the database. Results: There were 5846 patients ≥70yo (median age 77) and 15892 patients < 70 yo. Of the older ones, 245 (4.2%) were enrolled in a clinical trial in first line compared with 1602 (10%) for younger ones. Most of the older patients in this cohort (66%) had ER+ HER2+ disease, half had visceral metastases (< 3 metastatic sites in 82%). Median follow-up of older patients was 46.3 months; 95%CI 44.8-49.0. Cause of death was related to disease in 1155 (33.9%) older patients, and related to another cause or unknown in 2156 (63.3%), data were missing for 2441 patients. Median overall survival (OS) was 34.1 months in the older population, 95%CI 32.9-35.4, and specific overall survival was 70.8 months, 95%CI 66.3-80.0. Significant factors identified in the multivariable analysis for enrollment in 1st line treatment clinical trial ≥70 are shown in table. Volume of activity was not identified as one. By multivariate analysis, participation of older patients to a clinical trial was associated with an increased OS (HR 0.7; 95% CI 0.6-0.8) but not with a better breast cancer specific survival (HR 0.94; 95%CI 0.68-1.29). Conclusions: In this large real-life database, few older MBC patients were enrolled in a trial compared with younger ones. Factors associated with such participation to clinical research were younger age (< 80 yo), good PS, HER2+ disease, and investigational treatment consisting of chemotherapy or targeted therapy. There was a small improvement in accruing older patients between 2007-2011 and 2012-2016 (2.6% versus 5.5%). Most of these factors raise questions on drug availability and perceived potential benefits by investigators and medical teams. Accrual of older patients with cancer in other disease types should be more encouraged. VariableOR95%CIAge vs 70-75 75-80 80-85 85+0.74 0.47 0.170.54-1 0.31-0.71 0.06-0.37MBC diagnosis period vs 2008-2011 2012-20161.671.23-2.27Phenotype vs Others HER2+1.761.26-2.45PS vs 0 1 2-40.71 0.150.5-1 0.08-0.26Treatment4.88 5.253.08-7.9 3.48-8.14Chemotherapy vs others4.883.08-7.9Targeted treatment vs others5.253.48-8.14 Citation Format: Michael Bringuier, Matthieu Carton, Christelle Levy, Anne Patsouris, David Pasquier, Marc Debled, Olivier Rigal, William Jacot, Anthony Gonçalves, Isabelle Desmoulins, Thibault De La Motte Rouge, Thomas Bachelot, Jean-Marc Ferrero, Jean-Christophe Eymard, Florence Dalenc, Marie-Ange Mouret-Reynier, Thierry Petit, Michael Chevrot, Coralie Courtinard, Lionel Uwer, Jean-Sebastien Frenel, Capucine Baldini. Enrollment of older metastatic breast cancer patients in clinical trials [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-46.

Background: Prognosis of women with HER2+ metastatic breast cancer (MBC) has radically improved over the past 10 years, resulting from the implementation in clinical of anti-HER2 therapies. However, there are limited data regarding these trends in the older women, although they represent a growing segment of the population. Standard strategy being based mostly on combinations of anti-HER2 treatments with chemotherapy, under-treatment may be a specific issue in this population. Methods: Based on the ESME MBC Data Platform (NCT03275311),a unique national real-life database including individual data from all patients (pts) ≥18 years who initiated a first-line treatment for MBC between 2008 and 2016 in the 18 French Comprehensive Cancer Centers, the main objective of this work was the description of patients’ outcome in women with HER2+ MBC according to age: ≥70 vs Results: Of 22463 cases selected, 4045 (18%) women had HER2+ MBC with a 4.4-year median follow-up. Of those, 814 (20%) were aged ≥ 70 and had more often HR+ disease (Table 1). As 1st line treatment, anti-HER2 therapy was prescribed in 76% vs 92% of older vs younger pts, combined with chemotherapy in 65% vs 89%. Median OS and PFS (years) were 2.9 [2.6-3.1] and 0.9 [0.8 - 1.0] vs 4.5 [4.2-4.6] and 1.1 [1.1-1.2] in older vs younger patients. Multivariate analysis for OS identified the following variables as significant: age ≥ 70 (HR=1.57 IC95% [1.40-1.75]), 2 and ≥ 3 metastatic sites (HR=1.24 IC95% [1.10-1.39] and HR=1.92 IC95% [1.70-2.17] respectively), de novo MBC (HR 0.70 IC95% [0.63 - 0.77]), visceral disease with a time-varying effect (HR=2.67 IC95% [2.11-3.39] and 5.98 IC95% [4.64-7.46] at 1 and 5 years) and first-line treatment with a time-varying effect, better prognosis for combination of chemotherapy + anti-HER2 agent + endocrine therapy vs any other. Except for de novo MBC, similar results were observed for PFS. Conclusions: In this large real-life database, older HER2+ MBC patients received significantly less frequently “standard” first-line anti-HER2 treatment, defined as a combination of chemotherapy and anti-HER2 treatment. Age was a strong risk factor for both PFS and OS. Given the lack of information on geriatric assessment (e.g. general health status, functional status, comorbidity, etc.), confounding factors and usual selection biases cannot be ruled out. These results stress the importance to study older populations with specific approaches, not based on the usual transfer of those developed in younger ones, in order to avoid under and overtreatments, both that are not acceptable. Table 1: Patients’ characteristics and first-line treatment≥70 Citation Format: Mylène Annonay, Morgane Abiven, Etienne Brain, Mony Ung, Laurence Cristol-Dalstein, Marie-Ange Mouret-Reynier, Anthony Goncalves, Sophie Abadie-Lacourtoisie, Eric Francois, Claudia Lefeuvre-Plesse, Johann Le Fel, Veronique Lorgis, Veronique Servent, Lionel Uwer, Christelle Jouannaud, Marianne Leheurteur, Loic Campion, Coralie Courtinard, Olivier Villacroux, Thierry Petit, Pierre Soubeyran, Thomas Bachelot, Carine Bellera, Suzette Delaloge. Treatments and outcome in older versus younger women with HER2-positive metastatic breast cancer in the multicenter national observational ESME database [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 P1-19-19.

PURPOSE: A major question when treating HR+/HER2- metastatic breast cancer (MBC) is whether early introduction of chemotherapy (CT) increases endocrine resistance. We aimed to describe progression-free survival (PFS) under first endocrine therapy (ET) depending on whether given before or after CT in a large nationwide cohort, in the pre-CDK era. METHODS: The real-life retrospective ESME database includes all patients with MBC whose first-line treatment was initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres. Our primary objective was to compare PFS from start of first ET in patients with HR+/HER2- MBC who received ET or CT first. RESULTS: We identified 6293 patients who received at least one ET line during their first two therapeutic lines for MBC. As first-line therapy, 3832 (60.9%) received ET alone (ET1 1st group), whilst 2461 (39.1%) received CT, including 2024 patients (32.2%) with maintenance ET after CT (ET1 after CT group). Median PFS under first ET was 12.4 months (95% CI 11.9-13.1) in ET 1st group vs. 12.6 months in ET1 after CT group (95% CI 12.1-13.4), HR 0.96 (95% CI 0.90-1.01, P = 0.1277). CONCLUSIONS: PFS under first ET appears identical whether prescribed before or after chemotherapy. These data suggest chemotherapy does not promote endocrine resistance.

Prognostic significance of endometrioid epithelial ovarian cancer (EOC) is controversial. We compared clinical, pathological, and biological features of patients with endometrioid and serous EOC, and assessed the independent effect of histology on outcomes.We conducted a multicenter retrospective analysis of patients with EOC selected from the French Epidemiological Strategy and Medical Economics OC database between 2011 and 2016. Our main objective was to compare overall survival (OS) in endometrioid and serous tumors of all grades. Our second objectives were progression-free survival (PFS) and prognostic features.Out of 10,263 patients included, 3180 cases with a confirmed diagnosis of serous (N = 2854) or endometrioid (N = 326) EOC were selected. Patients with endometrioid histology were younger, more often diagnosed at an early stage, with lower-grade tumors, more frequently dMMR/MSI-high, and presented more personal/familial histories of Lynch syndrome-associated cancers. BRCA1/2 mutations were more frequently identified in the serous population. Endometrioid patients were less likely to receive chemotherapy, with less bevacizumab. After median follow-up of 51.7 months (95CI[50.1-53.6]), five-year OS rate was 81% (95CI[74-85]) in the endometrioid subgroup vs. 55% (95CI[53-57] in the serous subset (p0.001, log-rank test). In multivariate analyses including [age, ECOG-PS, FIGO, grade, and histology], the endometrioid subtype was independently associated with better OS (HR = 0.38, 95CI[0.20-0.70], p= 0.002) and PFS (HR = 0.53, 95CI[0.37-0.75], p0.001).Clinicopathological features at diagnosis are not the same for endometrioid and serous EOC. Endometrioid histology is an independent prognosis factor in EOC. These observations suggest the endometrioid population requires dedicated clinical trials and management.

Purpose: Older cancer patients are underrepresented in clinical trials. We aimed to understand barriers to clinical trial recruitment in women aged 70 years old (yo) or over with metastatic breast cancer (MBC).Methods: We used the national Epidemio-Strategy and Medical Economics MBC Data Platform, a French multi-center real life database. We selected MBC women over 70yo, without central nervous system metastases, with at least one line of systemic treatment, between January 1st, 2008 and December 31st, 2016, and had no other cancer in the 5 years before MBC. The primary objective was to evaluate the proportion of patients enrolled in clinical trials according to their age. Secondary objective was to identify variables associated with enrollment.Results: 5552 women were aged ≥ 70 (median 74yo; IQR72-77). 14611 were less than 70. Of the older ones, 239 (4%) were enrolled in a clinical trial during first line of treatment, compared with 1529 (10.5%) for younger ones. Multivariable analysis of variables predicting for enrollment during first line of treatment in older patients were younger age (OR 0.50 [95%CI; 0.33-0.76] for the 80-85yo class; OR 0.17 [95%CI; 0.06-0.39] for the 85yo and more class), good ECOG Performance Status (PS 0-1) (OR 0.15 [95%CI; 0.08-0.27] for the PS 2-4 class), HER2+ disease (OR 1.78 [95%CI; 1.27-2.48]), type of treatment (chemotherapy/targeted therapy/immunotherapy OR 5.01 [95%CI; 3.13-8.18]), and period (OR 1.65 [95%CI; 1.22–2.26] for 2012-2016, compared to 2008-2011).Conclusions: In this large database, few older MBC patients were enrolled in a trial compared with younger ones.

Older cancer patients are underrepresented in clinical trials. We aimed to evaluate the enrollment of older women aged 70 years old (yo) or over with metastatic breast cancer (MBC) in clinical trials.We used the national Epidemio-Strategy and Medical Economics MBC Data Platform, a French multi-center real-life database. We selected MBC women over 70yo, without central nervous system metastases, with at least one line of systemic treatment, between January 1st, 2008 and December 31st, 2016, and had no other cancer in the 5 years before MBC. The primary objective was to evaluate the proportion of patients enrolled in clinical trials according to their age. Secondary objective was to identify variables associated with enrollment in older ones.5552 women were aged ≥ 70 (median 74yo; IQR 72-77). 14,611 were less than 70. Of the older ones, 239 (4%) were enrolled in a clinical trial during first line of treatment, compared with 1529 (10.5%) for younger ones. Multivariable analysis of variables predicting for enrollment during first line of treatment in older patients were younger age (OR 0.50 [95%CI 0.33-0.76] for the 80-85yo class; OR 0.17 [95%CI 0.06-0.39] for the 85yo and more class), good ECOG Performance Status (PS 0-1) (OR 0.15 [95%CI 0.08-0.27] for the PS 2-4 class), HER2 + disease (OR 1.78 [95%CI 1.27-2.48]), type of treatment (chemotherapy/targeted therapy/immunotherapy OR 5.01 [95%CI 3.13-8.18]), and period (OR 1.65 [95%CI 1.22-2.26] for 2012-2016, compared to 2008-2011).In this large database, few older MBC patients were enrolled in a trial compared with younger ones.

Expression of hormone receptor (HR) for estrogens (ER) and progesterone (PR) and HER2 remains the cornerstone to define the therapeutic strategy for breast cancer patients. We aimed to compare phenotypic profiles between matched primary and metastatic breast cancer (MBC) in the ESME database, a National real-life multicenter cohort of MBC patients. Patients with results available on both primary tumour and metastatic disease within 6 months of MBC diagnosis and before any tumour progression were eligible for the main analysis. Among the 16,703 patients included in the database, 1677 (10.0%) had available biopsy results at MBC diagnosis and on matched primary tumour. The change rate of either HR or HER2 was 27.0%. Global HR status changed (from positive = either ER or PR positive, to negative = both negative; and reverse) in 14.2% of the cases (expression loss in 72.5% and gain in 27.5%). HER2 status changed in 7.8% (amplification loss in 45.2%). The discordance rate appeared similar across different biopsy sites. Metastasis to bone, HER2+ and RH+/HER2- subtypes and previous adjuvant endocrine therapy, but not relapse interval were associated with an HR discordance in multivariable analysis. Loss of HR status was significantly associated with a risk of death (HR adjusted = 1.51, p = 0.002) while gain of HR and HER2 discordance was not. In conclusion, discordance of HR and HER2 expression between primary and metastatic breast cancer cannot be neglected. In addition, HR loss is associated with worse survival. Sampling metastatic sites is essential for treatment adjustment.

Background Leptomeningeal metastasis (LM) is a rare complication of metastatic breast cancer (MBC), with high morbidity/mortality rates. Our study aimed to describe the largest-to-date real-life population of MBC patients treated with intrathecal (IT) therapy and to evaluate prognostic models. Methods The Epidemiological Strategy and Medical Economics (ESME) MBC database (NCT03275311) includes all consecutive patients who have initiated treatment for MBC since 2008. Overall survival (OS) of patients treated with IT therapy was estimated using the Kaplan–Meier method. Prognostic models were constructed using Cox proportional hazards models. Performance was evaluated using C-index and calibration plots. Results Of the 22 266 patients included in the database between 2008 and 2016, 312 received IT therapy and were selected for our analysis. Compared with non-IT-treated patients, IT-treated patients were younger at MBC relapse (median age: 52 years versus 61 years) and more often had lobular histology (23.4% versus 12.7%) or triple-negative subtype (24.7% versus 13.3%) (all P < 0.001). Median OS was 4.5 months [95% confidence interval (CI) 3.8-5.6] and 1-year survival rate was 25.6%. Significant prognostic factors associated with poorer outcome on multivariable analysis were triple-negative subtype (hazard ratio 1.81, 95% CI 1.32-2.47), treatment line ≥3 (hazard ratio 1.88, 95% CI 1.30-2.73), ≥3 other metastatic sites (hazard ratio 1.33, 95% CI 1.01-1.74) and IT cytarabine or thiotepa versus methotrexate (hazard ratio 1.68, 95% CI 1.28-2.22), while concomitant systemic therapy was associated with better OS (hazard ratio 0.47, 95% CI 0.35-0.62) (all P < 0.001). We validated two previously published prognostic scores, the Curie score and the Breast-graded prognostic assessment, both with C-index of 0.57. Conclusions MBC patients with LM treated with IT therapy have a poor prognosis. We could identify a subgroup of patients with better prognosis, when concomitant systemic therapy and IT methotrexate were used., Highlights • The outcome of BC patients with IT-treated LM is poor, with a median OS of 4.5 months. • Concomitant systemic therapy may improve the outcome in IT-treated patients. • Patients treated with IT methotrexate had better outcome than those treated with IT cytarabine/thiotepa. • The Curie and Breast-graded prognostic assessment scores were prognostic for IT-treated patients.

International audience; Eribulin mesylate (EM) was recently approved for metastatic breast cancer (MBC) chemotherapy (CT) in late lines by the FDA, with debated results in second line. We evaluated outcomes in breast cancer patients receiving EM as second, third and fourth line in a national real-life cohort of 16,703 consecutive MBC patients initiating their first metastatic therapeutic line between 2008 and 2014. Primary and secondary objectives were overall survival (OS) and progression-free survival (PFS). An imbalance was seen for HER2+ tumors and concomitant anti-HER2 targeted therapies use, we thus performed a subanalysis in HER2- patients. PFS and OS were significantly better in EM patients in third and fourth lines, compared to "Other chemotherapies" patients (PFS: 4.14 vs. 3.02 months, p = 0.0010; 3.61 vs. 2.53 months, p = 0.0102, third and fourth-line; OS: 11.27 vs. 7.65 months, p = 0.0001; 10.91 vs. 5.95 months, p

Background: Therapeutic options at diagnosis for metastatic breast cancers (MBC) differ largely according to cancer phenotype (namely, hormone receptor (HR) and HER2 status). Reported discordance rates between primary tumor and metastasis vary widely in literature, with a median of 18% for estrogen receptor, 31% for progesterone receptor and 10% for HER2. The present study aimed to compare phenotypic profiles between primary and MBC in the real-life setting. Patients (pts) and methods: Epidemio-Strategy and Medical Economics (ESME)MBC data platform (NCT03275311) is a French national, multicenter, observational cohort using clinical trials' methodology for data capture, monitoring and quality controls. At the time of analysis, it comprised data of 16703 consecutive newly diagnosed MBC pts (1/01/08-31/12/14) treated in 18 French comprehensive cancer centres. The primary endpoint was the discordance rate of HR and HER2 status between primary tumor and MBC (biopsy of metastatic site done within 6 months of MBC diagnosis). Only patients with both histological reports available were considered. Potential factors associated with phenotype discordance were assessed in a multivariate logistic regression. Results: 2933 out of 16703 (17.6%) had a biopsy in the first 6 months of metastatic disease. HR and/or HER2 status was available in 1677 pts. The discordance rate between primary and matched MBC was 14.2% (222/1566) for HR: loss of expression in 72.5%, gain in 27.5%. For HER2, the discordance rate was 7.8% (84/1076): 45.2% of losses and 54.8% of gains of expression. The primary HR+/HER2+ subgroup had the highest rate of changes: 53% (49/92) with either a loss of HR (43%), loss of HER2 (43%) or a loss of both (14%). 18% (33/181) of primary triple-negative breast cancer (TNBC) had a phenotypic change with a majority of HR gain (79%). In multivariate analysis, administration of adjuvant chemotherapy +/- targeted therapy was the sole independent predictor of HR status modification (OR: 1.73, 95%CI 1.27-2.36, p=0.001). The presence of a mixed histology was the only predictor of HER2 discordance (OR =2.57, 95%CI 1.19-5.55, p=0.016). Patient characteristics Total population (n=16703)Pts with primary and MBC phenotype available (n=1677)Age at metastatic diagnosis Median (range)61 (19-99)60 (24-93)De novo MBC4507 (27.1%)221 (13.2%)Number of metastatic sites Median (range)1 (1-9)2 (1-7)MBC sites Brain1200 (7.2%)138 (8.2%)Visceral7755 (46.4%)928 (55.3%)Non-visceral7748 (46.4%)611 (36.4%)Phenotypic profileN = 2933N=1677TNBC356 (18.5%)272 (19.3%)HR+/HER2-1251 (65.0%)917 (65.2%)HR-/HER2+150 (7.8%)105 (7.5%)HR+/HER2+168 (8.7%)112 (8%)Missing1008271Metastatic site samplingN=2933N=1677Bone692 (24.2%)419 (25.5%)Liver514 (18.0%)355 (21.6%)Skin379 (13.3%)203 (12.4%)Node306 (10.7%)169 (10.3%)Lung258 (9.0%)168 (10.2%)Pleura283 (9.9%)121 (7.4%)CNS/CSF*132 (4.6%)42 (2.6%)Other or multiple296 (10.3%)165 (10.0%)Missing7335* CNS= central nervous system, CSF=cerebro-spinal fluid Conclusion: Biopsy and phenotype re-evaluation of MBC early in the disease course has a confirmed potential significant therapeutic impact in this large scale real life setting and should be proposed as often as possible. Citation Format: Lefevre S, Lusque A, Joyon N, Arnould L, Penault-Llorca F, MacGrogan G, Treilleux I, Vincent-Salomon A, Haudebourg J, Maran-Gonzalez A, Charafe-Jauffret E, Courtinard C, Franchet C, Verriele V, Brain E, Tas P, Delaloge S, Filleron T, LaCroix-Triki M. Phenotypic discordance between primary and metastatic breast cancer (MBC) in a large scale real-life multicentre French cohort [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-12-05.

Background High Body mass index (BMI) is a risk factor for breast cancer among postmenopausal women and an adverse prognostic factor in early-stage. Little is known about its impact on clinical outcomes in patients with metastatic breast cancer (MBC). Methods The National ESME-MBC observational cohort includes all consecutive patients newly diagnosed with MBC between Jan 2008 and Dec 2016 in the 18 French comprehensive cancer centers. Results Of 22 463 patients in ESME-MBC, 12 999 women had BMI data available at MBC diagnosis. Median BMI was 24.9 kg/m2 (range 12.1–66.5); 20% of women were obese and 5% underweight. Obesity was associated with more de novo MBC, while underweight patients had more aggressive cancer features. Median overall survival (OS) of the BMI cohort was 47.4 months (95% CI [46.2–48.5]) (median follow-up: 48.6 months). Underweight was independently associated with a worse OS (median OS 33 months; HR 1.14, 95%CI, 1.02–1.27) and first line progression-free survival (HR, 1.11; 95%CI, 1.01; 1.22), while overweight or obesity had no effect. Conclusion Overweight and obesity are not associated with poorer outcomes in women with metastatic disease, while underweight appears as an independent adverse prognostic factor., Highlights • This is the first large multicenter cohort reporting BMI’s effect on outcomes among patients with metastatic breast cancer. • Overweight or obese status does not negatively influence outcome of metastatic breast cancer patients, whatever the subtype. • Underweight is a strong negative independent prognostic factor on outcomes, whatever the subtype.

Background Treatment strategies for metastatic breast cancer (MBC) have made great strides over the past 10 years. Real-world data allow us to evaluate the actual benefit of new treatments. ESME (Epidemio-Strategy-Medico-Economical)-MBC, a nationwide observational cohort (NCT03275311), gathers data of all consecutive MBC patients who initiated their treatment in 18 French Cancer Centres since 2008. Patients and methods We evaluated overall survival (OS) in the whole cohort (N = 20 446) and among subtypes: hormone receptor positive, human epidermal growth factor 2 negative (HR+/HER2−; N = 13 590), HER2+ (N = 3919), and triple-negative breast cancer (TNBC; N = 2937). We performed multivariable analyses including year of MBC diagnosis as one of the covariates, to assess the potential OS improvement over time, and we described exposure to newly released drugs at any time during MBC history by year of diagnosis (YOD). Results The median follow-up of the whole cohort was 65.5 months (95% CI 64.6-66.7). Year of metastatic diagnosis appears as a strong independent prognostic factor for OS [Year 2016 HR 0.89 (95% CI 0.82-0.97); P = 0.009, using 2008 as reference]. This effect is driven by the HER2+ subcohort, where it is dramatic [Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference]. YOD had, however, no sustained impact on OS among patients with TNBC [Year 2016 HR 0.93 (95% CI 0.77-1.11); P = 0.41, using 2008 as reference] nor among those with HR+/HER2– MBC [Year 2016 HR 1.02 (95% CI 0.91-1.13); P = 0.41, using 2008 as reference]. While exposure to newly released anti-HER2 therapies appeared very high (e.g. >70% of patients received pertuzumab from 2016 onwards), use of everolimus or eribulin was recorded in less than one-third of HR+/HER2– and TNBC cohorts, respectively, whatever YOD. Conclusion OS has dramatically improved among HER2+ MBC patients, probably in association with the release of several major HER2-directed therapies, whose penetrance was high. This trend was not observed in the other subtypes, but the impact of CDK4/6 inhibitors cannot yet be assessed., Highlights • OS of HER2+ MBC patients keeps improving over time [Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference]. • This effect seems timely related to the release of drugs demonstrated to improve survival in clinical trials. • OS gains observed in real life among HER2+ MBC patients are at least equivalent to those observed in clinical trials. • YOD had no sustained impact on OS among patients with TNBC and luminal MBC. • The impact of CDK4/6 inhibitors cannot yet be assessed in this cohort.

Patients with metastatic breast cancer (MBC) often require inpatient palliative care (IPC). However, mounting evidence suggests age-related disparities in palliative care delivery. This study aimed to assess the cumulative incidence function (CIF) of IPC delivery, as well as the influence of age.The national ESME (Epidemio-Strategy-Medical-Economical)-MBC cohort includes consecutive MBC patients treated in 18 French Comprehensive Cancer Centres. ICD-10 palliative care coding was used for IPC identification.Our analysis included 12,375 patients, 5093 (41.2%) of whom were aged 65 or over. The median follow-up was 41.5 months (95% confidence interval [CI], 40.5-42.5). The CIF of IPC was 10.3% (95% CI, 10.2-10.4) and 24.8% (95% CI, 24.7-24.8) at 2 and 8 years, respectively. At 2 years, among triple-negative patients, young patients (65 yo) had a higher CIF of IPC than older patients after adjusting for cancer characteristics, centre and period (65+/65: β = -0.05; 95% CI, -0.08 to -0.01). Among other tumour sub-types, older patients received short-term IPC more frequently than young patients (65+/65: β = 0.02; 95% CI, 0.01 to 0.03). At 8 years, outside large centres, IPC was delivered less frequently to older patients adjusted to cancer characteristics and period (65+/65: β = -0.03; 95% CI, -0.06 to -0.01).We found a relatively low CIF of IPC and that age influenced IPC delivery. Young triple-negative and older non-triple-negative patients needed more short-term IPCs. Older patients diagnosed outside large centres received less long-term IPC. These findings highlight the need for a wider implementation of IPC facilities and for more age-specific interventions.

Background Metastatic breast cancer (MBC) may require inpatient palliative care (IPC) but literature suggests age-related disparities in palliative care delivery. This study, based on real-world data, aimed to assess the cumulative incidence function (CIF) of IPC delivery and if age is an independent factor, taking into account the competing risk of death. Methods The national multicenter ESME (Epidemio-Strategy-Medical-Economical)-MBC cohort includes consecutive MBC patients treated in the 18 French Comprehensive Cancer Centers. IPC identification used ICD-10 palliative care coding. Main analysis first estimated pseudo values of 2-year and 8-year CIF of IPC. Linear regression models estimated the mean changes of pseudo-values (2 models: 2-year and 8-year CIF of IPC). Results Our analysis included 12375 patients, 5093 (41.2%) of whom were aged 65 or over. The median follow-up was 41.5 months (95% CI, 40.5-42.5). The CIF of IPC was 10.3% (95% CI, 10.2-10.4) and 24.8% (95% CI, 24.7-24.8) at two and eight years, respectively. At two years, among triple-negative patients, young patients ( Conclusions We found a relatively low CIF of IPC and that age influenced IPC delivery. Young triple negative and older non-triple negative patients needed more short-term IPC. Older patients diagnosed outside large centres received less long-term IPC. These findings highlight the need for a wider implementation of IPC facilities and for more age-specific interventions. Key messages Our study highlighted particular challenge for older MBC patients diagnosed outside large French Comprehensive Cancer Centers. By identifying age at MBC diagnosis as a factor of IPC delivery, this report supports a wider implementation of IPC facilities and more age-specific interventions.

The impact of locoregional treatment (LRT) on overall survival (OS) in de novo metastatic breast cancer (dnMBC) is still under debate, with very few data available regarding exclusive radiotherapy (ERT) as a therapeutic modality.We evaluated the impact of ERT, exclusive surgery, or a combination of surgery plus radiotherapy (bimodality therapy, BMT) on survival outcomes in a national real-life dnMBC cohort. The primary and secondary end points were OS and progression free survival (PFS) according to LRT (ERT, exclusive surgery, BMT) and no LRT. Sensitivity analyses were performed using propensity score matched analyses.From 2008 to 2014, 4507 dnMBC patients were identified. Only patients alive and free from progression under systemic therapy at least 1 year after diagnosis were included (n = 1965). Forty-five percent of patients (891/1965) underwent LRT: 41.1% (n = 366) ERT, 13.7% (n = 122) exclusive surgery, and 45.2% (n = 403) BMT. OS adjusted for major prognostic factors was significantly longer in the ERT and BMT group compared with no-LRT group, but not exclusive surgery (hazard ratio (HR) = 0.63, 95% confidence interval (CI) [0.49, 0.80], p 0.001, HR = 0.61, 95%CI [0.47, 0.78], p 0.001 and HR = 0.87, 95%CI [0.61, 1.26], p = 0.466 respectively). Results were similar after matching on a propensity score. ERT, surgery and BMT were all associated with a significantly better PFS in multivariable analysis.ERT was significantly associated with better OS in dnMBC, in the same magnitude as BMT, compared with no-LRT. However, even with statistical models adjusted for known prognostic factors and propensity score analysis, selection biases cannot be eliminated from observational studies.

Aim Real-world data inform the outcome comparisons and help the development of new therapeutic strategies. To this end, we aimed to describe the full characteristics and outcomes in the Epidemiological Strategy and Medical Economics (ESME) cohort, a large national contemporary observational database of patients with metastatic breast cancer (MBC). Methods Women aged ≥18 years with newly diagnosed MBC and who initiated MBC treatment between January 2008 and December 2016 in one of the 18 French Comprehensive Cancer Centers (N = 22,109) were included. We assessed the full patients’ characteristics, first-line treatments, overall survival (OS) and first-line progression-free survival, as well as updated prognostic factors in the whole cohort and among the 3 major subtypes: hormone receptor positive and HER2-negative (HR+/HER2−, n = 13,656), HER2-positive (HER2+, n = 4017) and triple-negative (n = 2963) tumours. Results The median OS of the whole cohort was 39.5 months (95% confidence interval [CI], 38.7–40.3). Five-year OS was 33.8%. OS differed significantly between the 3 subtypes (p Conclusions The ESME program represents a unique large-scale real-life cohort on MBC. This study highlights important situations of high medical need within MBC patients. Database registration clinicaltrials.gov Identifier NCT032753.

The aims of the present study were to describe treatment patterns and survival outcomes in patients with central nervous system metastases (CNSM) selected among metastatic breast cancer (MBC) patients included in a retrospective study from the Epidemiological Strategy and Medical Economics (ESME) MBC cohort.Neurological progression-free survival (NPFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Significant contributors to NPFS were determined using a multivariate Cox proportional hazards model.After a median follow-up of 42.8 months, of 16 701 patients included in the ESME MBC database, CNSM were diagnosed in 24.6% of patients. The most frequent treatments after diagnosis of CNSM were whole-brain radiotherapy (WBRT) (45.2%) and systemic treatment (59.3%). Median OS and NPFS were 7.9 months (95% CI: 7.2-8.4) and 5.5 months (95% CI: 5.2-5.8), respectively. In multivariate analysis, age70 years (vs50 years; HR = 1.40; 95% CI: 1.24-1.57), triple-negative tumours (vs HER2-/HR+; HR = 1.87; 95% CI: 1.71-2.06), HER2+/HR-tumours (vs HER2-/HR+; HR = 1.14; 95% CI: 1.02-1.27), ≥3 metastatic sites (vs 3; HR = 1.32; 95% CI: 1.21-1.43) and ≥3 previous treatment lines (vs 3; HR = 1.75; 95% CI: 1.56-1.96) were detrimental for NPFS. A time interval between selection and CNSM diagnosis superior to 18 months (vs9 months; HR = 0.88; 95% CI: 0.78-0.98) was associated with longer NPFS.This study describes current treatment patterns of MBC patients in a "real life" setting. Despite advances in stereotactic radiation therapy, most of the patients still received WBRT. More research is warranted to identify patient subsets for tailored treatment strategies.

Introduction/Background In SOLO1 trial, maintenance therapy with olaparib considerably improved progression-free survival (PFS) among women with newly-diagnosed, advanced BRCA-mutated HGEOC. Based on the large real-life ESME ovarian cancer (OC) cohort, we aimed to describe the patient‘s characteristics and survival outcomes of a selected cohort of BRCA-mutated patients before the era of PARP inhibitors maintenance in first line. Methodology ESME OC is a national cohort including all patients (pts) with EOC managed in the 18 French Comprehensive Cancer Centres (NCT03275298). ESME Research program collected retrospective data from patient‘s medical records. BRCA1, BRCA2, or both mutated patients with de novo diagnosed advanced (FIGO stage III or IV) high-grade serous or endometrioid EOC were eligible. Primary objective was to describe patient‘s characteristics, clinical features and treatment patterns. Results Of the 4777 patients with OC treated in first line by platinum-based chemotherapy between 2011 and 2016, 266 were included. Median age was 57.0 (33–81). 187 pts (70.3%) harbored a BRCA1 mutation, and 75 (28.2%) a BRCA2 mutation. 66.9% of patients had FIGO stage III disease. Almost all patients (95.5%) underwent surgical resection, after neoadjuvant chemotherapy (48%), or primary debulking surgery (44.9%). 119 pts (44.7%) received maintenance therapy and majority with bevacizumab alone (78.9%). After a median follow-up of 51.7months, the median PFS (mPFS) was 28.6months [95 CI: 26.2–32.4]. Patients exhibited higher mPFS in case of FIGO stage III than stage IV (32.4 months and 25.4 months, respectively), or BRCA2 mutation than BRCA1 (33.3 months and 27.7 months, respectively). Although populations were non comparable, mPFS was close between patients treated with or without maintenance (28.3 and 29.5 months, respectively). Median PFS2 were 51.4 months and 50.4 months, respectively. Estimated 5-year OS for the whole population was 69.2% [95 CI: 65.3–73.0]. Conclusion This large ESME OC cohort described clinical features and real-life survival outcomes among pts with newly diagnosed advanced BRCA-mutated HGEOC treated in specialized centres. Disclosure This work was supported by UNICANCER. The ESME OC database is supported by an industrial consortium (Roche, Pfizer, AstraZeneca, MSD, Eisai and Daiichi Sankyo). Data collection, analyses and publications are totally managed by R&D UNICANCER independently of the industrial consortium. All the authors declare that there is no conflict of interest regarding the publication of this article.

Background: In 2014, UNICANCER (composed of 18 French Comprehensive Cancer Centers) launched the Epidemiological Strategy and Medical Economics (ESME) program to investigate real-world data in solid tumors. Real-world data give the opportunity to assess for the activity of specific drugs outside clinical trials. Eribulin is approved for pre-treated metastatic breast cancer (MBC). Marketing authorization has been granted in France in July 2012. However few data are available regarding its efficacy in real life. We evaluated eribulin use as second and third line of chemotherapy in MBC patients from the ESME database. Methods: Data from all newly diagnosed MBC patients having initiated at least one treatment between Jan. 2008 and Dec. 2014 are included in the ESME database. Data were collected retrospectively using a clinical trial-like methodology. Primary endpoint was overall survival (OS), defined from the starting date of second or third line chemotherapy (eribulin versus other chemotherapy). Progression-free survival (PFS) was calculated as a secondary endpoint. Results: Of 16,703 MBC patients included in the ESME database, 7,412 received at least 2 lines of chemotherapy: eribulin/other chemotherapy, total 1,966/5,446, second line 363/5,446, third line 654/2,669. Depending on second or third line chemotherapy use classification, median age was 59 years (range 20-97) and 58 year (range 21 – 94), triple negative tumors accounted for 20% and 19% of cases, and median follow-up reached 26 months and 22 months respectively. Table reports median OS and PFS, according to lines and type of chemotherapy. OS eribulin (months)OS other chemotherapy (months)pPFS Eribulin (months)PFS other chemotherapy (months)pSecond line12.4 (11.3-15.1)11.8 (11.3-12.3)0.4654.1 (3.7-4.9)4.1 (4.0-4.3)0.9225Third line10.3 (9.3-11.5)7.7 (7.3-8.0) Supportive analyses (using a propensity score for adjustment and as a matching factor for nested case–control analyses) and sensitivity analyses will be available for full presentation at the meeting. Conclusion: In this large-scale real-life setting, MBC patients treated with third line eribulin showed an improved OS and PFS compared with those receiving another chemotherapy. The difference was not statistically significant for second line treatment. Citation Format: Jacot W, Heudel P-E, Fraisse J, Gourgou S, Guiu S, Dalenc F, Pistilli B, Campone M, Levy C, Debled M, Leheurteur M, Chaix M, Lefeuvre C, Goncalves A, Uwer L, Ferrero J-M, Eymard J-C, Petit T, Mouret-Reynier M-A, Courtinard C, Cottu P, Robain M, Mailliez A. Real-life activity of eribulin among metastatic breast cancer patients in the multicenter national observational ESME 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 P6-14-02.

Introduction Afin d’evaluer l’efficacite des traitements dans les essais cliniques randomises (ECR), la survie globale (SG), critere objectif et reproductible, est un critere reconnu en cancerologie par les autorites de sante. D’autres criteres sont egalement utilises, comme la survie sans progression (SSP), mais n’ont pas necessairement ete valides comme critere de substitution a la SG. L’objectif de ces criteres alternatifs est d’accelerer la mise a disposition des nouveaux traitements. A ce jour, dans le cancer du sein (CS) metastatique (m), la SSP et le temps jusqu’a progression (TJP) sont utilises. Les donnees de vie reelle (DVR) sont une source d’information majeure complementaire sur des populations peu representees dans les ECR (ex. : cancers rares, sujets âges) ou heterogenes. Les DVR permettent d’investiguer de multiples criteres d’evaluation de l’efficacite therapeutique et leur association avec la SG, etape necessaire lors de la validation des criteres de substitution. L’objectif de ce travail est double : decrire ces criteres alternatifs (SSP, TJP) a la SG ainsi le temps jusqu’au traitement suivant (TJTS) chez une cohorte de femmes atteints d’un CSm, et evaluer l’association au niveau individuel de ces criteres avec la SG. Methodes La plateforme de ESME CSm ( NCT03275311 ) centralise les DVR decrivant la prise en charge de femmes initiant le traitement d’un CSm a partir de 2008 dans les 18 centres de Lutte contre le cancer. La selection a porte sur les sujets ayant recu au moins une ligne de traitement et sans historique de cancer du sein controlateral avant le diagnostic metastatique, sur la periode 01/01/2008–31/12/2017. Les criteres ont ete decrits selon la methode de Kaplan–Meier. Les coefficients de correlation de Spearman entre les criteres de survie ont ete estimes par sous-type de cancer du sein (defini selon la presence des recepteurs hormonaux et l’expression de la proteine HER2) et selon le type de traitement recu en premiere ligne metastatique (1L). Resultats Parmi les 20 033 femmes incluses dans la population d’analyse, l’âge median etait de 60 ans. La mediane de suivi etait 62 mois (61,3–63,5). Chez les 2845 femmes avec un CSm de type triple negatif (TN) (14,2 %), la SG et la SSP variaient entre 13,5 (12,6–14,3) et 15,8 mois (14,9–17,7), et de 5,4 (5,1–5,8) et 6,5 mois (6,1–6,8), respectivement, selon le type de traitement. De plus, le coefficient de correlation etait de 0,72 (0,79–0,82) ou 0,82 (0,69–0,75) selon que les femmes etaient traitees par chimiotherapie (CT) ou par CT associee a une therapie ciblee respectivement suggerant une forte association au niveau individuel dans cette cohorte en vie reelle. Chez les 17 635 femmes ayant progresse en 1L, le TJP variait de 2,2 (1,8–3,5) a 8,2 mois (6,8–10,0). L’ensemble des criteres de survie ainsi que les associations avec la SG seront rapportes pour les autres sous-types de CS et selon les types de traitements en 1L. Conclusion A partir de DVR, nous avons decrit les principaux criteres de survie (SG, SSP, TJP, TJTS) utilises en cancerologie, de meme que l’association avec la SG de criteres alternatifs, pour chacun des sous-types de CS et selon differentes modalites de traitement en 1L. Ces resultats preliminaires pourront ainsi fournir les valeurs de reference dans le CSm. Par ailleurs, les donnees d’association individuelle permettront de generer des hypotheses quant aux proprietes de substitution a la SG de criteres alternatifs, a valider ulterieurement par des meta-analyses d’ECRs.

For luminal metastatic breast cancer (MBC), endocrine therapy (ET) is the recommended initial treatment before chemotherapy. Our objective was to evaluate the efficacy of multiple ET lines in a real-life study.The Breast Cancer Epidemiological Strategy and Medical Economics (ESME) project analysed data from all patients with systemic treatment for MBC initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres. The primary end-point was the successive progression-free survival (PFS) evaluation.The ESME research programme included 9921 patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2) negative (HER2-) MBC. Before any chemotherapy, 4195 (43.4%), 1252 (29.8%) and 279 (6.6%) patients received one, two or three ET ± targeted therapy, respectively. The median PFS for first-, second- and third-line ET ± targeted therapy was 11.5 (95% confidence interval [CI], 10.8-12.1), 5.8 (95% CI, 5.3-6.1) and 5.5 (95% CI, 4.6-6.3) months, respectively. In a multivariate analysis, time from diagnosis to metastatic recurrence (P 0.0001), presence of symptoms at metastatic relapse (P = 0.01), number of metastatic sites (P = 0.0003) and their localisation (P 0.0001) were prognostic factors for PFS1. Duration of previous PFS was the only prognostic factor for subsequent PFS (10% threshold). Ten percent of the patients showed long-term response to ET, with a total treatment duration before chemotherapy ≥43.6 months.Median PFS in our HR+/HER2- real-life cohort is similar to median first-line PFS reported in clinical trials, regardless of ET used as second- and third-line treatment. Despite the international consensus on early initiation of ET, the latter is not prescribed in most of the cases. Patients with a low tumour burden may achieve prolonged response on ET.

Background and Aims: Because of its low prevalence, metastatic breast cancer (MBC) in males is managed based on clinical experience with women. Using a real-life database, we aim to provide a comprehensive analysis of male MBC characteristics, management and outcome. Methods: The Epidemiological Strategy and Medical Economics Data Platform collected data for all men and women ⩾18 years with MBC in 18 participating French Comprehensive Cancer Centers from January 2008 to November 2016. Demographic, clinical, and pathological characteristics were retrieved, as was treatment modality. Men were matched 1:1 to women with similar characteristics. Results: Of 16,701 evaluable patients, 149 (0.89%) men were identified. These men were older (median age 69 years) and predominantly had hormone receptor HR+/HER2– disease (78.3%). Median overall survival (OS) was 41.8 months [95% confidence interval (CI: 26.9–49.7)] and similar to women. Median progression-free survival (PFS) with first-line therapy was 9.3 months [95% CI (7.4–11.5)]. In the HR+/HER2– subpopulation, endocrine therapy (ET) alone was the frontline treatment for 43% of patients, including antiestrogens ( n = 19), aromatase inhibitors ( n = 15) with luteinizing hormone-releasing hormone (LHRH) analogs ( n = 3), and various sequential treatments. Median PFS achieved by frontline ET alone was similar in men [9.8 months, 95% CI (6.9–17.4)] and in women [13 months, 95% CI (8.4–30.9)] ( p = 0.80). PFS was similar for HR+/HER2– men receiving upfront ET or chemotherapy: 9.8 months [95% CI (6.9–17.4)] versus 9.5 months [95% CI (7.4–11.7)] ( p = 0.22), respectively. Conclusion: MBC management in men and women leads to similar outcomes, especially in HR+/HER2– patients for whom ET should also be a cornerstone. Unsolved questions remain and successfully recruiting trials for men are still lacking.

Real-life analysis of overall survival (OS) trends among metastatic breast cancer (MBC) patients may help define medical needs and evaluate the impact of public health investments. The present study aimed to evaluate the independent impact of the year of MBC diagnosis on OS in the Epidemio-Strategy-Medical-Economical (ESME)-MBC cohort.ESME-MBC (NCT03275311) is a French, national, multicentre, observational cohort including 16,702 consecutive newly diagnosed MBC patients (01 January 2008-31 December 2014). Of 16,680 eligible patients, 15,085 had full immunohistochemistry data, allowing classification as hormone receptor-positive and HER2-negative (HR+/HER2-, N = 9907), HER2-positive (HER2+, N = 2861) or triple-negative (HR-/HER2-, N = 2317) subcohorts. Multivariate analyses of OS were conducted among the full ESME cohort and subcohorts.Median OS of the whole cohort was 37.22 months (95% confidence interval [CI], 36.3-38.04). Year of diagnosis was an independent predictor of OS (hazard ratio 0.98 [95% CI, 0.97-1.00], P = .01) together with age, subtype, disease-free interval, visceral metastases and number of organs involved. Median OS of HR+/HER2-, HER2+ and HR-/HER2- subcohorts was, respectively, 42.12 (95% CI, 40.90-43.10), 44.91 (95% CI, 42.51-47.90) and 14.52 (95% CI, 13.70-15.24) months. Year of diagnosis was a strong independent predictor of OS in HER2+ subcohort (hazard ratio 0.91 [95% CI, 0.88-0.94], P .001), but not in HR+/HER2- nor HR-/HER2- subcohorts (hazard ratio 1.00 [95% CI, 0.98-1.01], P = .80 and 1.00 [95% CI, 0.97-1.02], P = .90, respectively).The OS of MBC patients has slightly improved over the past decade. However, this effect is confined to HER2+ cases, highlighting the need of new strategies in the other subtypes.

Introduction Le cancer du sein est la tumeur la plus frequente chez la femme. Ces cancers peuvent etre metastatiques, soit de novo soit apres rechute d’une tumeur primitive. Les cancers du sein metastatiques (CSM) entrainent des situations palliatives. Les prises en charge palliatives interdisciplinaires (PPI) sont recommandees pour tous les patients avec cancer avance. Les recommandations preconisent d’integrer precocement les PPI dans le parcours de soins. Peu d’etudes existent sur le profil des patients qui y ont acces. L’objectif de cette etude etait de rechercher les determinants carcinologiques du recours aux PPI des patients atteints d’un CSM en tenant compte du risque de deces toutes causes. Methodes La cohorte de vie reelle ESME-CSM ( NCT03275311 ) inclut des patients primo-traites pour un CSM entre 2008 et 2015 dans 18 centres de lutte contre le cancer en France. Un echantillon a ete tire au sort pour cette analyse. L’evenement d’interet etait la premiere PPI (codee Z515 en diagnostic principal ou associe du resume standardise des sejours) depuis le diagnostic du CSM. Les variables explicatives etaient le profil moleculaire (statut hormonal + HER2) du cancer du sein, le grade tumoral, la realisation d’une chimiotherapie adjuvante, les antecedents de cancers autres, le statut metastatique (de novo ou rechute), le nombre de sites metastatiques (performance status, comorbidites et niveau socio-economique non disponibles). Un modele de Cox cause-specifique a ete utilise afin de prendre en compte le risque competitif de deces. Tous les risques relatifs (HR) ont ete ajustes sur l’âge, le centre et la periode. Resultats La population d’analyse comptait 2490 patients (representative de la population ESME globale). Les âges medians aux diagnostics de tumeur primitive et du CSM etaient respectivement de 54 ans et 61 ans. Un tiers des tumeurs etaient de grade eleve, 15 % de profil moleculaire triple negatif et pres de la moitie traitees par une chimiotherapie adjuvante. Un quart des CSM etaient metastatiques d’emblee. Parmi les patients, 37 % ont eu une PPI. Le delai median de PPI apres diagnostic etait de 1,7 an. La mediane de survie etait de 3,7 ans. Parmi les 1273 patients decedes, 61 % ont eu une PPI dont 77 % dans les trois derniers mois de vie. En analyse multivariee, les patients en rechute metastatique ou avec un profil moleculaire triple negatif, un cancer de grade III ou un antecedent de chimiotherapie adjuvante sur la tumeur primitive avaient un risque plus important de necessiter une PPI que les patients atteints de tumeur moins graves. Les antecedents de cancer et l’âge modifiaient l’effet du profil moleculaire. Le risque d’avoir recours a une PPI etait plus eleve uniquement pour les patients avec profil moleculaire triple negatifs sans antecedent d’autre cancer. Enfin, en cas de sites metastatiques multiples, le risque de necessiter une PPI semblait plus eleve la premiere annee de suivi que les annees suivantes. Conclusion Les facteurs de mauvais pronostic des CSM sont associes a un risque plus important de recours a une PPI au cours du suivi. Le recours aux PPI reste partiel et tardif. Des PPI precoces impliquant moins de trois professionnels (donc non codees en Z515) ainsi qu’une externalisation de patients sur d’autres etablissements pourraient en partie expliquer ce resultat. Des analyses complementaires avec modeles multi-etats sont en cours. Elles pourraient confirmer ces resultats sur l’ensemble de la cohorte ESME-CSM.

Introduction In 2014, the RD IV should not be correlated to the output (OS) and affect the OS only indirectly through its effect on the treatment. We used “Activity level of FCCC”, which represents the number of cases in the whole database per contributing FCCC as IV with five strata. Analysis was carried out with the two-stage residual inclusion method (2SRI). For the quasi-trial analysis, the idea is to use a “superficial” randomized trial using variables, for example centers, reflecting a definite preferences for certain treatment options. Indeed, comparisons of results between centers can be informative and it is likely such differential preferences exist in real-life practice. In this study, we have considered the percentage of patients with bevacizumab + paclitaxel in each center, regardless of treatment arm. Results In the first analysis published by Delaloge and al., the OS adjusted for major prognostic factors was significantly longer in the paclitaxel and bevacizumab group compared with paclitaxel [hazard ratio (HR) 0.672, 95 % confidence interval (CI) 0.601–0.752] [1] . Using IV method to support these results seems difficult due to the lack of candidate variables. The level of activity of FCCC, with five strata, leads to different conclusions compared with those obtained in Delaloge's paper. Conclusion For the quasi-trial analysis, the percentage of patients with bevacizumab + paclitaxel had an independent and significant impact on OS [HR = 0.180, CI = 0.043–0.748]. Centers in which more than 50 % of the patients were reintroduced had an adjusted HR for OS of [HR = 0.735, CI = 0.645–0.837] compared with centers in which 50 % or less of patients were treated with bevacizumab + paclitaxel. These results consolidate those obtained with a conventional multivariate Cox model.

Introduction Le programme Epidemio-Strategie et Medico-Economique (ESME), centralise les donnees cliniques, et therapeutiques de patients traites pour un cancer donne. Dans les centres volontaires, la selection des patients tend a l’exhaustivite par l’utilisation d’une approche multi-source et le retour systematique au dossier medical garantissant qualite et validite des donnees. Le premier volet concerne les patients traites pour cancer du sein metastatique (CSM). Cette cohorte represente 35 % des patients traites en France mais n’est pas representative du niveau national. La cohorte Cancer de l’INCa est constituee de tous les patients atteints d’un cancer en France depuis 2010 ayant entraine des soins a l’hopital, en ville, ou la mise en affection de longue duree (ALD). Les donnees collectees sont issues du Systeme national des donnees de sante. Un travail a ete amorce entre l’INCa et Unicancer afin d’identifier des parametres pour extrapoler au niveau national les resultats issus de la cohorte ESME CSM. Methodes La premiere etape a consiste a reconstruire, a partir de la cohorte Cancer, une cohorte de patients ayant un CSM diagnostique en 2013 (maximum 36 mois apres le primitif) et dont le premier traitement a ete realise dans un Centre de lutte contre le cancer (CLCC). Les patients ont ete identifies via les codes diagnostics issus du PMSI et de l’ALD, et les traitements via le PMSI et les donnees de remboursement de ville. Resultats Sur l’annee 2013, respectivement 1225 et 1319 patients avec un CSM ont ete identifies dans la cohorte ESME CSM et la cohorte Cancer. Les caracteristiques des patients et de leur traitement sont decrites. Discussion La population des patients ayant eu un CSM en 2013 (tumeur primitive en 2011, 2012 ou 2013) identifiee a partir de la cohorte Cancer est plus faible (−7,1 %). Les caracteristiques des patients et de leur maladie sont coherentes entre les deux echantillons en tenant compte du decalage des effectifs lies a la difference entre les dates de reference utilisees par les deux cohortes (date de diagnostic clinique versus date de premiere prise en charge). Pour cette population specifique, des variables liees au patient, aux metastases et a l’etablissement de traitement permettront de definir des parametres d’extrapolation des resultats issus de la cohorte ESME CSM. Conclusion Ces resultats encouragent a identifier des parametres d’extrapolation des resultats de la cohorte ESME CSM. La meme demarche sera adoptee sur les deux autres cohortes du programme ESME.

Introduction En oncologie, l’indice fonctionnel ECOG (PS), echelle de mesure de l’etat de sante general des patients, est un facteur pronostique systematiquement pris en compte dans les essais cliniques. Dans la pratique medicale courante, le PS est utilise par le medecin pour adapter la strategie therapeutique mais non systematiquement documente dans le dossier medical du patient. Le PS ne pouvant etre reporte retroactivement, la construction d’un substitut du PS permettrait de prendre en compte ce facteur dans les analyses sur donnees longitudinales retrospectives en vie reelle. L’objectif de ce travail etait de construire un substitut du PS a partir d’informations disponibles (âge, comorbidites, constantes biologiques) et decrire la performance du modele de prediction. Methodes A partir de la plateforme epidemio-strategie et medico-economique (ESME) des CLCCs sur le cancer du sein metastatique (CSM), les donnees de 865 patients traites dans quatre centres pour leur maladie metastatique a partir de 2014 ont ete extraites. Un recueil retrospectif a ete a ete organise concernant les comorbidites de Charslon et des valeurs biologiques (hematologie et biochimie). Un modele de regression logistique a ete utilise pour predire le substitut du PS. Les variables utilisees pour predire le PS etaient : l’âge, le statut menopausique, le score de Charslon, les transaminases, la bilirubine, la creatinine, les LDH, l’hemoglobine et les lymphocytes. Le PS a ete evalue selon deux seuils (PS > 0 et PS > 1). La performance du modele a ete utilisee par la methode de l’aire sous la courbe de ROC. Resultats Une mesure du PS au diagnostic de la maladie metastatique etait documentee chez 28 % seulement des 865 patients identifies. Les 619 patients sans mesure du PS ont ete exclus de l’analyse (316 patients sans aucune mesure du PS disponible dans le dossier medical et 303 patients avec une mesure du PS non disponible au diagnostic metastatique). Les patients exclus etaient un peu plus âges (63,2 versus 60,0, p 0 pour lequel l’âge (OR = 1,01 ; IC95 % [1,02–1,09]) et la bilirubine (OR = 8,01 ; [1,31–50,40]) etaient significativement associes. Les memes variables ont ete suggerees a partir d’une cohorte de validation externe comprenant 164 patients malgre une performance peu informative (AUC Conclusion Ce premier travail sur la prediction d’un substitut du PS suggere l’âge et un marqueur hepatique comme variables candidates pour integrer le modele de prediction. Malgre son utilisation courante dans le domaine de la prediction, le score de Charlson n’a pas ete retenu dans le modele final. L’evaluation de la performance du modele etait moyennement informative. Une etude prospective avec un effectif plus important et au diagnostic du cancer du sein metastatique, une mesure systematique du PS, l’administration d’un questionnaire de qualite de vie et la collecte de constantes biologiques permettrait de confirmer ces resultats.

Background Bevacizumab combined with paclitaxel as first-line chemotherapy for patients with HER2-negative metastatic breast cancer (MBC) has led to mixed results in randomized trials, with an improvement in progression-free survival (PFS) but no statistically significant overall survival (OS) benefit. Real-life data could help in assessing the value of this combination. Patients and methods This study aimed to describe the outcome following first-line paclitaxel with or without bevacizumab in the French Epidemiological Strategy and Medical Economics (ESME) database of MBC patients, established in 2014 by Unicancer. The primary and secondary end points were OS and PFS, respectively. Results From 2008 to 2013, 14 014 MBC patient files were identified, including 10 605 patients with a HER2-negative status. Of these, 3426 received paclitaxel and bevacizumab (2127) or paclitaxel (1299) as first-line chemotherapy. OS adjusted for major prognostic factors was significantly longer in the paclitaxel and bevacizumab group compared with paclitaxel [hazard ratio (HR) 0.672, 95% confidence interval (CI) 0.601–0.752; median survival time 27.7 versus 19.8 months]. Results were consistent in all supportive analyses (using a propensity score for adjustment and as a matching factor for nested case–control analyses) and sensitivity analyses. Similar results were observed for the adjusted PFS, favoring the combination (HR 0.739, 95% CI 0.672–0.813; 8.1 versus 6.4 months). Conclusions In this large-scale, real-life setting, patients with HER2-negative MBC who received paclitaxel plus bevacizumab as first-line chemotherapy had a significantly better OS and PFS than those receiving paclitaxel. Despite robust methodology, real-life data are exposed to important potential biases, and therefore, results need to be treated with caution. Our data cannot therefore support extension of current use of bevacizumab in MBC.

Introduction Les donnees de « vie reelle » sont des donnees cliniques et therapeutiques recueillies a grande echelle pour decrire la prise en charge reelle des patients et ses resultats. Ces donnees sont complementaires a celles des essais cliniques, chaque approche ayant son interet. L’exhaustivite de la population selectionnee est un point majeur pour la validite des donnees de vie reelle et repose sur une methodologie de selection parfois complexe. Methodes La selection des patients dans le premier projet ESME, patients avec une premiere prise en charge entre 2008 et 2013 pour un cancer du sein metastatique (CSM) dans les 20 sites des 18 centres de lutte contre le cancer (CLCC), a ete realisee a partir de differentes sources d’information structurees ou non structurees : programme medicalise des systemes d’information (PMSI), dossier pharmaceutique, bases locales specifiques, base des reunions de concertation pluridisciplinaire (RCP), moteurs de recherche internes. La qualification de chaque type de liste a ete prealablement realisee sur echantillons avant de decider l’utilisation de la source d’information dans la demarche. Les listes de preselection issues des differentes sources utilisees ont ete fusionnees afin de constituer une liste unique. La methodologie maximisait la sensibilite tout en essayant de conserver une bonne specificite. Le retour systematique aux Dossiers patients informatises (DPI) a permis de valider la selection de chaque patient. Des controles qualites des cas non selectionnes et selectionnes ainsi qu’un audit du processus complet de selection ont ete realises. Resultats Au total 34 484 patients ont ete preselectionnes. Ce travail de selection a necessite de s’appuyer sur les outils et les informations accessibles dans les centres. Apres retour a l’ensemble des dossiers des patients preselectionnes, 14 022 patients ont effectivement ete selectionnes. La contribution des sources de preselection a la selection finale est decrite dans la Tableau 1 . La proportion de patients effectivement selectionnes (40,7 %) differait d’un centre a l’autre (28 % a 58 %), cependant, le nombre final de patients effectivement selectionnes dans chaque centre correspondait a l’estimation initiale faite pour chaque centre a partir d’informations extrapolees du PMSI national. Conclusion L’utilisation de sources d’information differentes etait indispensable pour selectionner l’ensemble des patients de notre population, en particulier ceux suivis uniquement en consultation et accessibles a partir des moteurs de recherche uniquement. Le taux de conversion preselection/selection etait globalement inferieur a celui attendu. Nous considerons cependant avoir approche l’exhaustivite des patients a selectionner par l’approche multi-sources. Nous avons utilise les sources d’information communes a l’ensemble des centres et les sources d’information additionnelles propres aux centres afin de maximiser la sensibilite globale de la demarche. Cette methodologie de selection menee avec l’ensemble des sources d’information disponibles, variable d’un centre a l’autre, dont plusieurs sont standardisees dans tous les centres, possede une sensibilite tres elevee mais implique de poursuivre le travail pour ameliorer la specificite des patients preselectionnes et minimiser le travail de validation du dossier.

1078 Background: Real-life data may help checking that public investments match closely medical needs. During the last decade, several drugs have been released on the market for MBC on the basis of a potential impact on overall survival (OS). Based on the large real-life ESME cohort, we aimed to describe the time evolution of MBC OS according to main phenotypes. Methods: ESME is a unique MBC national cohort including all consecutive patients (pts) who initiated treatment for MBC between 1/01/08 and 31/12/14 in the 18 French comprehensive cancer centres. ESME collects retrospective data using clinical trial-like methodology including quality assessments. Database lock was 8/12/2016. Primary objective was the impact of year of MBC diagnosis on OS. Multivariate Cox regressions were used with adjustment for main prognostic covariates. Results: 15170 out of 16703 pts in ESME had full IHC data allowing their classification as HR+HER2- (N=9922), HER2+ (N=2863), or HR-HER2- (N=2321) cases. Median FU and OS for the whole cohort are 4.05 yrs [95 CI: 3.98-4.12], and 3.1 yrs [95 CI: 3.03-3.18] respectively. In the adjusted multivariate analysis, year of MBC diagnosis, age at MBC, subtype (using HER2+ as reference), disease-free interval (DFI), visceral involvement, and number (nbr) of metastatic sites are significant OS predictors (table) although with low effect for the first item. Age at MBC, DFI, visceral involvement, and nbr of metastatic sites remained significant prognostic variables in subtypes. Year of diagnosis was no longer significant in HR+HER2- nor HR-HER2- cases (HR=0.997, p=0.71 and HR=0.997, p=0.84), while it was highly significant in HER2+ cases (HR=0.91, p

1052 Background: For HR+/HER2– metastatic breast cancer (mBC), International guidelines recommend multiple lines of endocrine therapy (ET) before starting chemotherapy. Few studies have assessed the efficacy of such strategy on large populations. Our objective was to evaluate multiple ET activity according to clinical and biological characteristics and type of ET. Methods: All patients (pts) who initiated treatment for a newly diagnosed mBC between January 2008 and December 2014 in all 18 French Comprehensive Cancer Centers were included in the real life ESME database. ESME collects retrospective data using a clinical trial-like methodology. Database lock was 8 Dec 2016. Primary endpoint of the current study was progression free survival (PFS) on successive ET lines. Only pts with ET alone were assessed (pts receiving ET after chemotherapy as maintenance therapy, or combined with targeted treatment were excluded). Results: 9921 pts out of 16703 in ESME, had HR+/HER2- mBC (median age 62.0 years[range 23-96]). 53.9% of pts had visceral and 80.1% non visceral disease at diagnosis. Median OS of HR+/HER2- pts was 42.15 months (95% CI, 40.93-43.27). As first-line therapy, 4123 pts (41.6%) received ET alone, while 2038 received chemotherapy alone (20.5%) and 3667 received both (37%). Median PFS for first-line ET (N=4123) was 11.3 months (95% CI, 10.6-11.9). Only 668 pts (16%) received subsequent lines of ET alone. Types of ET used are described in the table below. Successive PFS will be reported at the meeting. Conclusions: Those data show that ET is prescribed to less than 50% of patients with HR+/HER2- mBC in first line and only to a small minority in subsequent lines. This is not in line with existing guidelines (NCCN, ABC3). Real-life median PFS for first-line ET is consistent with median PFS reported in clinical trials (Nabholtz, 2000). [Table: see text]

Introduction Les donnees de vraie vie (RWD) ont un role important pour l’evaluation de l’efficience des medicaments et des strategies therapeutiques, et ce en complement des donnees provenant des essais cliniques controles. La methodologie de constitution de la plateforme de RWD ESME repose sur une approche multi sources pour centraliser et standardiser les donnees nationales relatives a la prise en charge (PEC) des patients dans les 18 centres de lutte contre le cancer. Methodes La plateforme ESME, geree par R&D Unicancer, integre des variables issues de bases de donnees structurees (donnees relatives aux sejours hospitaliers et donnees sur les medicaments dispenses dans les centres), ainsi que des donnees non structurees issues du dossier patient informatise (DPI). L’integration des donnees du DPI implique une relecture systematique par des techniciens d’etudes cliniques specifiquement formes, tenant compte si disponibles des donnees des bases locales (donnees des bases RCP, donnees issues de l’enquete permanente cancer si poursuivie…). La plateforme pour laquelle la gestion de l’anonymat est geree centre par centre, regroupe l’ensemble des donnees anonymisees consolidees des differentes sources. Cette methodologie fait l’objet de controles qualite, d’audit interne sur le recueil et de constitution de listes de preselection, ainsi que de controles de data-management systematiques. Les donnees collectees sont mises a jour annuellement et la plateforme integre les donnees des patients nouvellement diagnostiques. Resultats et discussion Le premier volet de ce programme concerne la plateforme ESME « Cancer du sein metastatique » (CSM) pour laquelle les dossiers de 16 736 patients ont ete selectionnes et valides. L’objectif final est de 25 000 dossiers completes valides attendus d’ici 2019. Il etait important de pouvoir capter les patients PEC pour un CSM non hospitalises et ne recevant pas de traitement dans le centre. Environ 12 % ont ainsi ete identifies comme etant exclusivement pris en charge par des therapies orales ou hormonotherapie avec un suivi en consultation dans les centres. Le controle qualite (CQ) sur site du processus de selection a ete realise chez environ 20 % des dossiers non selectionnes, et 13 % des dossiers selectionnes ont ete controles manuellement pour certains criteres majeurs. Ces criteres seront detailles avec les taux d’erreurs par critere et leurs implications pour l’exploitation des donnees. La plateforme ESME constitue une source unique en Europe de donnees en vie reelle pour la PEC du CSM. Elle est accessible a l’interrogation par des equipes de recherche ou des partenaires industriels, apres validation des questions de recherche par le comite scientifique ESME (CSE), sous le controle d’un comite de deontologie et d’un comite consultatif international (dix projets de recherche sont actuellement en cours). Conclusion La plateforme ESME constituera a terme une source unique et independante d’analyse de donnees dans une grande variete de pathologies d’organes ou de domaines therapeutiques en oncologie. Elle pourra contribuer a une meilleure comprehension de l’utilisation des strategies therapeutiques en vraie vie ainsi que leurs determinants. Ces donnees peuvent guider la communaute scientifique vers une prise de decision adaptee au contexte et ameliorer la PEC du patient en oncologie.