399P - Treatment patterns and outcomes in HER2-low, HR+ metastatic breast cancer patients previously treated with endocrine therapy in the United States

Background

Over half of human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancers (mBC) are now recognized as HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+ and in situ hybridization [ISH−]). DESTINY-Breast06 (NCT04494425) is assessing if trastuzumab deruxtecan (T-DXd) can replace a first line of metastatic chemotherapy following endocrine therapy (ET) in hormone receptor positive (HR+), HER2-low patients (pts). We report results from an observational, retrospective analysis used to understand the characteristics and outcomes of a real-world (rw) United States cohort of HR+, HER2-low mBC pts who initiated a chemotherapy-based line of therapy (LOT) in the mBC setting.

Methods

The analysis used the nationwide Flatiron Health electronic health record-derived de-identified database (01/01/2011–08/31/2023). Eligible HR+, HER2-low pts initiated chemotherapy (index LOT) after ≥2L ET or ≤6 months (m) of 1L ET + cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) in the mBC setting. This cohort met additional inclusion/exclusion criteria similar to the DB-06 trial. Rw overall survival (rwOS), time to treatment discontinuation or death (rwTTD/D), and time to next treatment or death (rwTTNT/D) from start of the index LOT (index date) were assessed using Kaplan-Meier analysis with corresponding 95% confidence intervals (CI).

Results

At index date, median age of final cohort (N=963) was 64 years; 271 (28.1%) were categorized as de novo stage IV. 131 (13.6%) pts received second line chemotherapy (index LOT) within 6m of initiating first line treatment with ET+CDK4/6i; 832 (86.4%) pts received chemotherapy after two or more prior lines of ET. The most common chemotherapy (index LOT) was capecitabine (45.2%). From index date, median rwOS was 18.7m (95% CI: 17.3–20.2), median rwTTD/D was 4.9m (95% CI: 4.6–5.2) and median rwTTNT/D was 5.6m (95% CI: 5.3–6.0).

Conclusions

This study provides insight into the clinical characteristics and outcomes of a large rw cohort of HR+, HER2-low pts initiating chemotherapy following ET in the mBC setting. The findings underscore the poor disease prognosis and limited efficacy of chemotherapy-based regimens for pts who have progressed on ET regimens.

Clinical trial identification

Editorial acknowledgement

Medical writing support was provided by Lillian Dukes and Marielle Brown of Costello Medical (Boston MA, USA) and funded by Daiichi Sankyo.

Legal entity responsible for the study

Daiichi Sankyo.

Funding

Daiichi Sankyo, AstraZeneca.

Disclosure

S. Modi: Financial Interests, Institutional, Research Grant: AstraZeneca, Daiichi Sankyo, Duality Bio, Genentech, Nuvation, Seagen; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Daiichi Sankyo, Duality Bio, Eli Lilly, Genentech, Gilead, GSK, Macrogenics, Seagen; Financial Interests, Personal, Other, Support for attending meetings and/or travel: AstraZeneca, Daiichi Sankyo, Seagen. D. Byng: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo Europe GmbH. S. Zhang: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc. Y. Xiong: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc. S. Hunter: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc. A. Struebing: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo Europe, GmbH. K. Dunton: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo UK Ltd. Z. Mbanya: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. W. Jacot: Financial Interests, Institutional, Research Grant: AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, BMS, Daiichi Sankyo, Eisai, Lilly (France), MSD, Novartis, Pfizer, Roche, Seagen; Financial Interests, Personal, Other, Support for attending meetings and/or travel: AstraZeneca, Chugai, Eisai, GSK, Lilly (France), Novartis, Pfizer, Pierre Fabre, Roche, Sanofi Aventis; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Daiichi Sankyo, Eisai, Gilead, Lilly (France), MSD, Novartis, Pfizer, Roche, Seagen.