Abstract P1-19-19: Treatments and outcome in older versus younger women with HER2-positive metastatic breast cancer in the multicenter national observational ESME database
Authors: Annonay Mylène , Abiven Morgane , Brain Etienne , Ung Mony , Cristol-Dalstein Laurence , Mouret-Reynier Marie-Ange , Goncalves Anthony , Abadie-Lacourtoisie Sophie , Francois Eric , Lefeuvre-Plesse Claudia , Fel Johann Le , Lorgis Veronique , Servent Veronique , Uwer Lionel , Jouannaud Christelle , Leheurteur Marianne , Campion Loic , Courtinard Coralie , Villacroux Olivier , Petit Thierry , Soubeyran Pierre , Bachelot Thomas , Bellera Carine , Delaloge Suzette 
Published: March 2020

Abstract
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 &lt;70. Secondary objective included the description of treatment patterns and a multivariate analysis. Outcome was described with overall survival (OS) and progression-free survival (PFS). Variables of interest were age (≥70 vs &lt; 70), number of metastatic sites at initial MBC diagnosis (1 vs 2 vs ≥3), visceral disease (Y/N), hormone receptor status (HR+/HR-), de novo MBC (Y/N), type of first-line treatment. We relied on Cox’s proportional hazard (PH) model, with adjustment for non-PH in the presence of time-varying effects; hazard ratios (HR) with 95% confidence interval were reported (IC95%).
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&lt;70AllP value N814 (20%)3231 (80%)4045 (100%)NAAge at MBC diagnosis (years)median775357NAQ1-Q373-8245-6047-67HR+ (≥10%)Yes560 (69%)2034 (63%)2594 (64%)0.01No247 (30%)1167 (36.1%)1414 (35%)missing7 (1%)30 (1%)37 (1%)De novo MBCYes310 (38%)1310 (41%)1620 (40%)0.20No503 (62%)1915 (59%)2418 (60%)missing1 (0%)6 (0%)7 (0%)Number of metastatic sites1429 (53%)1670 (52%)2099 (52%)0.902211 (36%)834 (26%)1045 (26%)3+170 (21%)696 (21%)866 (21%)missing4 (0%)31 (1%)35 (1%)Visceral diseaseYes510 (63%)2096 (65%)2606 (64%)0.18No300 (37%)1104 (34%)1404 (35%)Missing4 (0%)31 (1%)35 (1%)Chemotherapy + anti-HER2 agent as 1st line treatmentYes529 (65%)2880 (89%)3409 (84%)&lt;0.01No241 (30%)296 (9%)537 (13%)Missing44 (5%)55 (2%)99 (2%)Anti-HER2 agent as 1st line treatmentYes623 (76%)2984 (92%)3607 (89%)&lt;0.01No147 (18%)192 (6%)339 (8%)Missing44 (6%)55 (2%)99 (3%)
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.