Association of Endocrine Therapy for HR+/ERBB2+ Metastatic Breast Cancer With Survival Outcomes

Abstract

Importance: Evidence suggests that patients with human epidermal growth factor receptor 2-positive (ERBB2+ [formerly HER2+]) metastatic breast cancer (MBC) have different clinical characteristics and outcomes according to their hormone receptor (HR) status. The place of endocrine therapy (ET) for patients with HR+/ERBB2+ is still not clearly defined in this setting.

Objective: To evaluate the association of HR status and first-line inclusion of ET with outcomes among patients with ERBB2+ MBC.

Design, setting, and participants: This cohort study was an analysis of clinical data from the French clinical Epidemiological Strategy and Medical Economics (ESME) cohort, including patients with MBC who started treatment between 2008 and 2017. The last date of follow-up was June 18, 2020. Data were analyzed from May 2021 to May 2022.

Exposures: Patients were treated with first-line ERBB2-targeted therapy and either chemotherapy (CT) with or without ET or ET alone. For the study of the association of maintenance ET with outcomes, we included patients treated with first-line ERBB2-targeted therapy with CT and with or without maintenance ET.

Main outcomes and measures: Median overall survival (OS) and median first-line progression-free survival (PFS) were reported using the Kaplan-Meier method. Cox proportional hazards models and a propensity score were constructed to report and adjust for prognostic factors. Multivariable analysis included age at MBC, time to MBC, number of metastatic sites, type of metastases, and Eastern Cooperative Oncology Group performance status.

Results: Among 4145 women with ERBB2+ MBC, 2696 patients had HR+ (median [IQR] age, 58.0 [47.0-67.0] years) and 1449 patients had HR- (56.0 [47.0-64.0] years) tumors. The median OS for patients with HR+ vs HR- tumors was 55.9 months (95% CI, 53.7-59.4 months) vs 42.0 months (95% CI, 38.8-45.2 months), confirmed in multivariable analysis (hazard ratio, 1.40; 95% CI, 1.26-1.56; P < .001). The median PFS for patients with HR+ vs HR- tumors was 12.2 months (95% CI, 11.5-12.9 months) vs 9.8 months (95% CI, 9.2-11.0 months; P = .01), and the HR was 1.15 (95% CI, 1.06-1.26; P < .001). In multivariable analysis, no significant difference was found in OS or PFS for 1520 patients treated with ERBB2-targeted therapy with CT and with or without ET vs 203 patients receiving ERBB2-targeted therapy with ET, regardless of type of ERBB2-targeted therapy (trastuzumab or trastuzumab with pertuzumab). This result was confirmed by matching patients using a propensity score. Using the time-dependent ET variable among patients with ERBB2-targeted therapy with CT, those with maintenance ET had significantly better PFS (hazard ratio, 0.70; 95% CI, 0.60-0.82; P < .001) and OS (hazard ratio, 0.47; 95% CI, 0.39-0.57; P < .001).

Conclusions and relevance: These results suggest that ET-containing first-line regimens may be associated with benefits among a subgroup of patients with HR+/ERBB2+ MBC.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Diéras reported receiving personal fees from Roche Genentech, Novartis, Lilly, MSD, Pfizer, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Seagen, Eisai, and Pierre Fabre Oncologie outside the submitted work. Dr Petit reported receiving personal fees from Pfizer, Lilly, Novartis, AstraZeneca, Daiichi Sankyo, and Seagen outside the submitted work. Dr Gonçalves reported receiving research funding to the Institut Paoli-Calmettes from MSD, Bristol Myers Squibb, Novartis, Boerhinger Roche, Sanofi, Daiichi Sankyo, and AstraZeneca and personal fees to the Institut Paoli-Calmettes from MSD, Seagen, and Novartis. Dr Augereau reported receiving grants to the Institut de Cancerologie de l'Ouest, Angers from GSK, AstraZenca and Daiichi Sankyo, Novartis, and Seagen outside the submitted work. Dr Bachelot reported receiving grants from Seagen, AstraZeneca, and Novartis and personal fees from Pfizer, Seagen, AstraZeneca and Daiichi Sankyo, Novartis, and Lilly outside the submitted work. Dr Pistilli reported receiving grants from Daiichi Sankyo; grants to Gustave Roussy from AstraZeneca, Gilead Sciences, Novartis, Seagen, Lilly, MSD, and Daiichi Sankyo; and travel expenses from AstraZeneca, Pierre Fabre, and MSD outside the submitted work. Dr Frenel reported receiving personal fees from Pfizer, Seagen, Novartis, AstraZeneca, Clovis Oncology, GSK, Daiichi Sankyo, Roche, and Lilly outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Patient Flowchart

ERBB2 indicates human epidermal growth factor receptor 2 (formerly HER2); ESME, Epidemiological Strategy and Medical Economics; HR, hormone receptor; NA, not applicable.

Figure 2.. Kaplan-Meier Survival Plots by Hormone Receptor (HR) Status

PFS indicates progression-free survival; OS, overall survival.

Figure 3.. Kaplan-Meier Survival Plots by Treatment Subgroup and After Propensity Score Matching

Propensity score matching was done 1:1 between patients who were treated with human epidermal growth factor receptor 2 (ERBB2, formerly HER2)–targeted therapy (trastuzumab or trastuzumab and pertuzumab [T+P]) with chemotherapy (CT) and with or without endocrine therapy (ET) and patients with ERBB2-targeted therapy with ET only. OS indicates overall survival; PFS, progression-free survival.