About 20% of breast cancer (BC) patients will develop distant metastases. HER2-positive (HER2+) disease is associated with poorer prognosis. However, outcome of HER2+ BC patients has dramatically improved since the use of trastuzumab. Although most HER2+ metastatic BC (MBC) patients will eventually develop progressive disease within one year of trastuzumab-based treatment, some are long-term responders (LTR). Few data on these patients are available.
The primary objective was to assess overall survival (OS) of HER2+ MBC patients treated with trastuzumab as 1st-line at the Institut Curie, based on institution-specific data included in the French Epidemiological Strategy and Medical Economics (ESME) program for MBC patients established in 2014 by Unicancer. Long-term responders (LTR) were defined as having a non-progressive disease for at least 2 years under 1st-line trastuzumab. Secondary objectives included progression-free survival (PFS), disease-free interval (DFI), prediction factors for LTR status by univariate and multivariate analysis: characteristics of patients (age, BMI, menopausal status), of primary tumour (e.g. hormone receptor (HR) status), of treatment (e.g. endocrine therapy, partner for trastuzumab combination), number and type of metastases.
From 2008 to 2014, 2990 MBC patients were identified in the Curie-ESME MBC database. Of these, 460 had HER2+ disease. Sixteen patients with second primary malignancy were excluded. Of the 444 remaining patients, 340 received 1st-line trastuzumab and could be analyzed. With a 42.5-month median follow-up time, the mean age at metastatic diagnosis was 55.7 years, 59.4% had a HR-positive disease and 43.2% had de novo metastases or occurring within 6 months after adjuvant treatment. DFI was >24 months in 47.9% of patients, and 78.5% received 1st-line trastuzumab combined with taxane-based chemotherapy (CT).
In 87 patients (25.6%) classified as LTR, median PFS was 56.2 months (CI95% 41.53-not reached) vs. 10.9 months in non-LTR (CI95% 9.46-11.8). Median OS in LTR is not reached versus 44.3 months in non-LTR (CI95% 37.9-49.1).
Median age, menopausal status, BMI, pathological characteristics and treatment for primary BC were similar in both groups.
The following factors were predictive of LTR status by univariate analysis: number of metastatic sites (<3 versus > 3, p=0.022); endocrine treatment for metastatic disease (p=0.002); absence of central nervous system metastases (p=0.035); and taxane-based 1st- line CT (p=0.032). In multivariate analysis, only number of metastatic sites and taxane-based 1st-line CT were predictive of LTR status.
In contrast, age, DFI, visceral disease, and adjuvant trastuzumab-based treatment did not influence outcome. Although not statistically significant, HR+ status was more frequent in LTR versus non-LTR patients (66.7% versus 56.9%).
With a median follow-up of 42.5 months, we found that more than 95% of LTR to 1st-line trastuzumab were still alive and could achieve a median PFS longer than 4.6 years. Although some clinical factors are clearly associated with better outcome, further investigations are needed to identify the mechanisms of resistance or sensitivity to trastuzumab.
Citation Format: Kaczmarek E, Saint-Martin C, Pierga J-Y, Brain E, Rouzier R, Dubot C, Savignoni A, Mouret-Fourme E, Simon G, Carton M, Lerebours F. Long-term survival in HER2-positive metastatic breast cancer treated with first-line trastuzumab: Real-life results from the Curie ESME database [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 P5-21-14.