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.

Keywords: Anti-HER2; Metastatic breast cancer; OS; PFS; Real-world; Treatment patterns.

Fig. 1

Patient disposition in the study and vital status at study inclusion. ^aAccording to the screening log, 47 patients met the study eligibility criteria but were not included in the study because they could not be reached, or they refused to provide consent. ^bViolation of eligibility criteria. Abbreviations: 2/3/4/5/6/7/8/9/10LT, second-/third-/fourth-/fifth-/sixth-/seventh-/eighth-/ninth-/tenth-line treatment; N, number of patients; pt(s), patient(s)

Fig. 2

HR and HER2 status before 2LT initiation for MBC. a Setting of testing, sample of origin and positivity; b HR status based on most recent assessment. ^aER and PgR status was unknown for one and two patients, respectively, and not included in the denominator; the sample origin was the primary tumor in all cases. ^bAlthough the results of HER2 testing was negative for one patient, the patient had undergone an additional two HER2 testings, one prior (primary tumor) and one after (metastatic site) 2LT initiation, both with a positive results, hence this patient was retained in the study. Abbreviations: 2/3LT, second-/third-line treatment; dnMBC, de novo MBC; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; MBC, metastatic breast cancer; N, total number of patients; n, number of patients with indicated characteristics; PgR, Progesterone receptor; rMBC, recurrent MBC; unk, unknown

Fig. 3

Treatments for HER2+ MBC in terms of pharmacological categories, per line of treatment. a Frequency of treatments; b Patters of treatments. Numbers next to bars indicate: % (95% CI). Abbreviations: 2/3/4L, second-/third-/fourth line; 2LT/3LT/4LT, second-/third-/fourth-line treatment; CI, confidence interval; HER2, human epidermal growth factor receptor 2; mAb, monoclonal antibody; MBC, metastatic breast cancer; N, number of patients with available data; n, number of patients with indicated characteristics

Fig. 4

KM-estimated rw-PFS, rw-PFS2 and OS in HER2-positive MBC patients initiating 2LT. a PFS from 2LT initiation until progression or all-cause death; b PFS from 2LT initiation until progression or all-cause death, among patients treated with the most prevalent 2LT regimen; c PFS2 from 2LT initiation until progression on 3LT or all-cause death, among patients who advanced to 3LT; d OS from 2LT initiation until all-cause death; e PFS from 3LT initiation until progression or all-cause death; f PFS from 4LT initiation until progression or all-cause death. Abbreviations: 2/3/4L, second-/third-/fourth-line; CI, confidence interval; HER2, human epidermal growth factor receptor 2; KM, Kaplan–Meier; mAb, monoclonal antibody; MBC, metastatic breast cancer; OS, overall survival; P, progression; PFS, progression-free survival; rw, real-world

Fig. 5

Swimmer plot showing individual patient characteristics with respect to HER2 retesting, treatment type, and disease progression for patients who underwent HER2 retesting and had different results. *Treatment was discontinued for reason other than PD or unknown reason. **This patient underwent 5 different HER2 testings after initiation of 2LT but only 2 are shown in the plot: an uncertain result was obtained ~ 12 months after 2LT initiation, which was followed by a negative result after 15 days (the latter is shown on the plot) and the next result was ~ 6 months later which was uncertain (not shown on the plot) and was followed by 2 negative results after 6 days, both on the same day (the latter are shown on the plot as one timepoint). ***Start date and end date of 2LT was the same. For this patient, death without PD was recorded