ENDOCRINE RESISTANCE AND REAL-WORLD TREATMENT PATTERNS AFTER FIRST-LINE (1L) ET+CDK4/6I IN HR+/HER2-METASTATIC BREAST CANCER (MBC)
Author(s)
Thao Vo, PhD1, Nina Balanchivadze, MD2, Paul R. Conkling, MD3, Preeti Sudheendra, MD1, Paolo D'Amico, MD1, Ila Sruti, MPH3, Junxin Shi, PhD3, Ping Shi, PhD3, Kim M. Hirshfield, MD, PhD1;
1Merck & Co. Inc., Rahway, NJ, USA, 2Virginia Oncology Associates, Norfolk, VA, USA, 3Ontada, Boston, MA, USA
1Merck & Co. Inc., Rahway, NJ, USA, 2Virginia Oncology Associates, Norfolk, VA, USA, 3Ontada, Boston, MA, USA
OBJECTIVES: ET+CDK4/6 is the mainstay for HR+/HER2- mBC, yet >50% of patients develop resistance. This study aims to understand their patient and treatment characteristics, stratified by ET resistance status.
METHODS: Adults with HR+/HER2- mBC from 02/2015-01/2023 within The US Oncology Network, whose cancer progressed on 1L ET+CDK4/6 inhibitor, were selected based on a stratified random sample of their second-line (2L) treatment: chemotherapy (CT) or antibody-drug conjugate (ADC); ET monotherapy; Other 2L; or No 2L. Endocrine resistance was categorized as primary (PR) or secondary (SR), per 5th ESO-ESMO guidelines.
RESULTS: 430 patients were included (PR:220; SR:210) with median age of 67 years. De novo mBC was observed in 44.4% (PR:35.0%; SR:54.3%), and 53.7% had visceral involvement (PR:54.5%; SR:52.9%). Among patients who progressed from early-stage diagnosis to mBC, 28.4% received neoadjuvant therapy, while 72.4% received adjuvant therapy (PR:76.1%; SR:65.8%), predominantly ET-based. Median duration of 1L CDK4/6i was 5.1 (PR) and 20.5 (SR) months. Numbers of patients with PR:SR receiving 2L CT/ADC (0% ADC), 2L ET monotherapy (73.7% SERD), Other 2L (95.2% ET+targeted therapy), No 2L were 82:40, 22:35, 44:82, 72:53, respectively. Common “Other 2L” regimens included ET+CDK4/6i (58.9%) or ET+everolimus (21.8%). 38.4% received 3L treatment, of which 57.6% had CT/ADC (PR:67.9%; SR:46.9%). Differences in frequency of CT/ADC use between PR:SR narrowed in subsequent lines.
CONCLUSIONS: mBC patients have distinct real-world treatment trajectories, based on ET resistance status. PR was linked to shorter 1L duration, frequent adjuvant ET exposure, and earlier transition to CT/ADC. SR was associated with more de novo metastatic disease and frequent use of Other 2L, primarily ET-based combinations with targeted therapies. These findings underscore an unmet need for resistance-informed treatment sequencing to improve outcomes and optimizing resource utilization in HR+/HER2- mBC.
METHODS: Adults with HR+/HER2- mBC from 02/2015-01/2023 within The US Oncology Network, whose cancer progressed on 1L ET+CDK4/6 inhibitor, were selected based on a stratified random sample of their second-line (2L) treatment: chemotherapy (CT) or antibody-drug conjugate (ADC); ET monotherapy; Other 2L; or No 2L. Endocrine resistance was categorized as primary (PR) or secondary (SR), per 5th ESO-ESMO guidelines.
RESULTS: 430 patients were included (PR:220; SR:210) with median age of 67 years. De novo mBC was observed in 44.4% (PR:35.0%; SR:54.3%), and 53.7% had visceral involvement (PR:54.5%; SR:52.9%). Among patients who progressed from early-stage diagnosis to mBC, 28.4% received neoadjuvant therapy, while 72.4% received adjuvant therapy (PR:76.1%; SR:65.8%), predominantly ET-based. Median duration of 1L CDK4/6i was 5.1 (PR) and 20.5 (SR) months. Numbers of patients with PR:SR receiving 2L CT/ADC (0% ADC), 2L ET monotherapy (73.7% SERD), Other 2L (95.2% ET+targeted therapy), No 2L were 82:40, 22:35, 44:82, 72:53, respectively. Common “Other 2L” regimens included ET+CDK4/6i (58.9%) or ET+everolimus (21.8%). 38.4% received 3L treatment, of which 57.6% had CT/ADC (PR:67.9%; SR:46.9%). Differences in frequency of CT/ADC use between PR:SR narrowed in subsequent lines.
CONCLUSIONS: mBC patients have distinct real-world treatment trajectories, based on ET resistance status. PR was linked to shorter 1L duration, frequent adjuvant ET exposure, and earlier transition to CT/ADC. SR was associated with more de novo metastatic disease and frequent use of Other 2L, primarily ET-based combinations with targeted therapies. These findings underscore an unmet need for resistance-informed treatment sequencing to improve outcomes and optimizing resource utilization in HR+/HER2- mBC.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
HSD89
Topic
Health Service Delivery & Process of Care
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Oncology