Abstract PO3-04-11: Unmet clinical need in patients with pre-treated hormone receptor-positive/HER2-negative (HR+/HER2–) metastatic breast cancer in routine care: a targeted literature review
Authors: Spring Laura , Collin Simon M , Dhillon Inderjit K , Long Gráinne , Bertranou Evelina , Jhaveri Komal , Bardia Aditya 
Published: May 2024

Abstract
Background Treatment options remain limited to chemotherapy (CT) for patients with HR+/HER2− metastatic breast cancer (MBC) who have progressed on endocrine therapy (ET) with/without CDK4/6 or PI3K pathway inhibitors (i). We aimed to review the current unmet need in patients who had received ≥ 1 prior systemic therapy in terms of ET resistance as well as CT survival outcomes, tolerability and discontinuation. Methods MEDLINE, Embase and the Cochrane Library were searched via Ovid for observational studies (≥ 50 patients who had received ≥ 1 prior systemic therapy, January 2018 – January 2023). Abstracts from relevant congresses (January 2021 – February 2023) were reviewed. All screening was performed in a single-blind manner by one reviewer and any uncertainties were resolved by a senior reviewer. Results We included 72 full-text publications and 48 congress abstracts (US based 39%, European 28%, Asian 23%).
Median treatment duration was 1.9–16.2 months (m) for ET (7 studies) and 2.0–24.5 m for ET-based therapy (5 studies). Exceptional responders (10% of patients treated for the longest time) received ET for ≥ 43.6 m (1 study, N = 4195).
The proportion of patients with ET-resistant disease ranged widely (3–100%; 22 studies) and increased by line (L) of therapy: 14–19% of patients treated in 1L had primary resistance, 14–49% in ≥ 2L and 27–68% in ≥ 3L; acquired resistance was reported for 26–38% of patients in 1L, 51–57% in ≥ 2L, 32–60% in ≥ 3L (2 studies).
One or more prior lines of CT had a negative impact on median overall survival (mOS; 5 studies) and median progression-free survival (mPFS; 11 studies) in subsequent therapy lines regardless of the chosen treatment; prior CT had no effect on mOS in 3 studies, no effect on mPFS in 4 studies.
Consecutive CT cycles (primarily after ET + CDK4/6i) steadily lost clinical benefit (Table), with mPFS with 2 to 5 lines of CT: 7.6 m, 4.8 m, 4.2 m and 3.2 m, and mOS: 13.5 m, 9.1 m, 6.8 m and 7.2 m, respectively (1 study, N = 266). Paclitaxel + bevacizumab as second CT had a mPFS and a mOS of 8.6 m and 19.8 m, respectively (1 study, N = 538). Eribulin use in ≥ 2L had a mPFS of 4.6–10.0 m (2 studies) and a mOS of 10.1–11.2 m (2 studies). Patients who progressed on CDK4/6i as best response and those with a mPFS of &lt; 6 m on ET benefited more from CT than ET in ≥ 2L with a mPFS of 7.1–8.1 m compared with 1.7–3.9 m, respectively (2 studies).
Discontinuation due to toxicity was 2–36% (3 studies) for CT in 2L and dose reduction was required in 19–37% of patients (2 studies). Common grade 3/4 adverse events in patients receiving CT were leukopenia (17%), neutropenia (7%), thrombocytopenia (3%) and pneumonitis (1–3%) (3 studies). Conclusions Our review of real-world evidence highlights the limitations of repeated CT for patients with ET-resistant HR+/HER2− MBC, characterized by diminishing clinical benefit and significant toxicity burden. Results are limited by treatment and study population heterogeneity. Clinical outcomes are expected to improve with the use of new therapies, for which real-world evidence has yet to accrue.
Table Real-world clinical outcomes with chemotherapy from observational studies CI, confidence interval; CT, chemotherapy; L, line; mOS, median overall survival; mPFS, median progression-free survival; NR, not reported
Citation Format: Laura Spring, Simon M Collin, Inderjit K Dhillon, Gráinne Long, Evelina Bertranou, Komal Jhaveri, Aditya Bardia. Unmet clinical need in patients with pre-treated hormone receptor-positive/HER2-negative (HR+/HER2–) metastatic breast cancer in routine care: a targeted literature review [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-04-11.