TREATMENT PATTERNS AND OUTCOMES IN PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER TREATED WITH FIRST-LINE TAXANE, TRASTUZUMAB, AND PERTUZUMAB: A 2012-2024 US REAL-WORLD ANALYSIS
Author(s)
Arielle L. Heeke, MD1, Chloe Spalding, PhD2, Danalyn Byng, PhD3, Sabrina Wang, PharmD4, Arthur Allignol, PhD3, Shannon Hunter, MS4, Mackenzie Henderson, PharmD4, William Jacot, MD, PhD5.
1Department of Cancer Medicine, Atrium Health Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, NC, USA, 2Daiichi Sankyo UK Ltd, Uxbridge, United Kingdom, 3Daiichi Sankyo Europe GmbH, Munich, Germany, 4Daiichi Sankyo, Inc, Basking Ridge, NJ, USA, 5Institut du Cancer de Montpellier, INSERM U1194, Montpellier University, Montpellier, France.
1Department of Cancer Medicine, Atrium Health Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, NC, USA, 2Daiichi Sankyo UK Ltd, Uxbridge, United Kingdom, 3Daiichi Sankyo Europe GmbH, Munich, Germany, 4Daiichi Sankyo, Inc, Basking Ridge, NJ, USA, 5Institut du Cancer de Montpellier, INSERM U1194, Montpellier University, Montpellier, France.
OBJECTIVES: Trastuzumab + pertuzumab + taxane (THP) became standard-of-care first-line (1L) treatment for human epidermal growth factor 2 (HER2)-positive metastatic breast cancer (mBC) in 2012, following results from CLEOPATRA (NCT00567190). The ongoing DESTINY-Breast09 (DB-09) trial (NCT04784715) is evaluating trastuzumab deruxtecan (T-DXd) ± pertuzumab versus THP in 1L for HER2-positive mBC. To contextualize contemporary real-world outcomes, this retrospective study examined long-term outcomes for patients who initiated 1L THP and met key DB-09 criteria.
METHODS: We used the nationwide Flatiron Health electronic health record-derived de-identified mBC database (observation period: 01/01/2012-03/31/2025) to select patients with HER2-positive mBC who received 1L THP and met key DB-09 criteria. Propensity score weighting was applied to create a cohort with observed baseline characteristics aligned to the THP arm of DB-09. Real-world overall survival (rwOS), progression-free survival (rwPFS), time to treatment discontinuation or death (rwTTD/D), and time to next treatment or death (rwTTNT/D) from THP initiation were estimated using weighted Kaplan-Meier methods with 95% confidence intervals (CI).
RESULTS: Overall, 943 patients with HER2-positive mBC met key DB-09 criteria. After weighting, the cohort size was 365 (sum of weights=364.7), effective sample size was 664.7, and median follow-up was 57.5 months (m). In the weighted cohort, 215 patients progressed to 2L (42.0% trastuzumab emtansine [T-DM1]-based, 20.1% T-DXd-based) and 121 patients to 3L (22.1% T-DXd-based, 17.6% trastuzumab-based, 9.9% T-DM1-based); 150 (41.0%) patients did not transition to 2L due to death or censoring. From 1L THP initiation, median (95% CI) rwOS was 78.1m (69.1-91.2), rwPFS was 17.2m (15.2-20.1), rwTTD/D was 17.5m (15.7-21.0), and rwTTNT/D was 21.3m (18.0-24.1).
CONCLUSIONS: In this contemporary real-world cohort treated with 1L THP for HER2-positive mBC, rwOS exceeded historical benchmarks, potentially reflecting the use of effective subsequent lines of therapy. In contrast, rwPFS appeared broadly unchanged, highlighting the need to optimize 1L disease control and delay progression.
METHODS: We used the nationwide Flatiron Health electronic health record-derived de-identified mBC database (observation period: 01/01/2012-03/31/2025) to select patients with HER2-positive mBC who received 1L THP and met key DB-09 criteria. Propensity score weighting was applied to create a cohort with observed baseline characteristics aligned to the THP arm of DB-09. Real-world overall survival (rwOS), progression-free survival (rwPFS), time to treatment discontinuation or death (rwTTD/D), and time to next treatment or death (rwTTNT/D) from THP initiation were estimated using weighted Kaplan-Meier methods with 95% confidence intervals (CI).
RESULTS: Overall, 943 patients with HER2-positive mBC met key DB-09 criteria. After weighting, the cohort size was 365 (sum of weights=364.7), effective sample size was 664.7, and median follow-up was 57.5 months (m). In the weighted cohort, 215 patients progressed to 2L (42.0% trastuzumab emtansine [T-DM1]-based, 20.1% T-DXd-based) and 121 patients to 3L (22.1% T-DXd-based, 17.6% trastuzumab-based, 9.9% T-DM1-based); 150 (41.0%) patients did not transition to 2L due to death or censoring. From 1L THP initiation, median (95% CI) rwOS was 78.1m (69.1-91.2), rwPFS was 17.2m (15.2-20.1), rwTTD/D was 17.5m (15.7-21.0), and rwTTNT/D was 21.3m (18.0-24.1).
CONCLUSIONS: In this contemporary real-world cohort treated with 1L THP for HER2-positive mBC, rwOS exceeded historical benchmarks, potentially reflecting the use of effective subsequent lines of therapy. In contrast, rwPFS appeared broadly unchanged, highlighting the need to optimize 1L disease control and delay progression.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO203
Topic
Clinical Outcomes, Real World Data & Information Systems
Disease
Oncology