Real-world management strategies and clinical outcomes of metastatic HER2-positive breast cancer in Greece in the second-line setting and beyond (the togetHER study).

Abstract

Background: In the realm of HER2-positive (HER2+) metastatic breast cancer (MBC), the advent of targeted therapies, notably trastuzumab and pertuzumab, represents a substantial advancement in enhancing patient outcomes. However, the intricacies of treatment escalate when patients encounter progression or resistance during first-line (1L) therapy. The togetHER study aimed to elucidate real-world insights into the profile, management strategies, and outcomes for HER2+ MBC patients initiating second-line treatment (2LT) in Greece, predating recent international guideline changes incorporating trastuzumab deruxtecan and tucatinib in the second line and beyond lines of treatments.

Methods: Data from adult female patients with HER2+ MBC who had initiated 2LT between 01-Jan-2015 and 31-Dec-2018 in 18 oncology departments across Greece were retrospectively abstracted through medical chart review.

Results: The eligible population comprised 122 patients, 68.0% of whom presented with recurrent MBC. Among the latter, 26.5% were tested for HER2 both in early and metastatic settings with 27.3% of them changing HER2 status from negative to positive. Retesting of HER2 expression following 2LT initiation was recorded in 8 cases. At 2LT initiation, patients' median age was 57.0 years and 63.6% were hormone receptor-positive. The most common metastatic sites were bone (56.6%), lung (44.3%), liver (41.0%), and brain (29.5%). Anti-HER2 agent usage in 1L and 2L stood at 91.8% and 92.6%, respectively, with rates slightly diminishing in third (3L) (85.9%) and fourth line (4L) (82.4%). Endocrine therapy administration was generally low across treatment lines (12.3%, 9.9%, and 5.9%, in 2L, 3L, and 4L respectively), while chemotherapy use increased from 30.3% in 2L to 47.9% and 47.1% to 3L and 4L, correspondingly. Median progression-free survival (PFS) for 2L, 3L, and 4L was 7.7 [95% confidence interval (CI) 6.0-14.4], 6.4 (95% CI 5.4-7.1), and 5.6 (95% CI 2.6-9.0) months, respectively, while median overall survival was 25.0 (95% CI 20.5-34.4) months.

Conclusions: Although the 2LT pattern in Greece generally aligned with guidelines, persistently poor treatment outcomes underscore a significant unmet medical need for these patients.