Association Between Event-Free/Distant Relapse-Free Survival and Overall Survival in Patients With Early-Stage Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer
Author(s)
Aurelien Jamotte, MSc1, Jagadeswara Rao Earla, PharmD, MBA, PhD2, Amin Haiderali, MBBS, MBA, MPH3, Amit Ahuja, M.Pharm4, Sakshi Jindal, M.Pharm4, Kanupriya Mahajan, M.Pharm4, Aniket Sharma, M.Pharm4, Ioana Gulas, MSc5, Jane Candlish, MSc, PhD6, Tracy Westley, MScPH7;
1MSD Innovation & Development GmbH, Zurich, Switzerland, 2Merck & Co., Inc., Rahway, NJ, USA, 3Merck & Co., Inc., North Wales, PA, USA, 4Lumanity, Gurugram, India, 5Lumanity, Toronto, ON, Canada, 6Lumanity, Sheffield, United Kingdom, 7Lumanity, Bethesda, MD, USA
1MSD Innovation & Development GmbH, Zurich, Switzerland, 2Merck & Co., Inc., Rahway, NJ, USA, 3Merck & Co., Inc., North Wales, PA, USA, 4Lumanity, Gurugram, India, 5Lumanity, Toronto, ON, Canada, 6Lumanity, Sheffield, United Kingdom, 7Lumanity, Bethesda, MD, USA
OBJECTIVES: Establishing validated surrogate endpoints for overall survival (OS) can support early evaluation of clinical benefits and accelerated regulatory approval. We aimed to evaluate the surrogate relationship between event-free survival (EFS) or distant relapse-free survival (DRFS) with OS in patients with high risk, early-stage hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer.
METHODS: The systematic literature review (SLR) identified studies reporting EFS, DRFS, and OS in patients with HR+/HER2- breast cancer in the neoadjuvant/adjuvant treatment setting, focusing on neoadjuvant chemotherapy followed by surgery and adjuvant endocrine therapy (± adjuvant chemotherapy). Published real-world evidence and randomized controlled trials were assessed for suitability in the surrogacy outcome analysis, considering study design, population heterogeneity, endpoint definitions, and data maturity. Both trial-level and arm-level surrogacy were considered. Weighted linear regression analyses were planned based on landmark EFS/DRFS and OS rates to explore arm-level association between EFS/DRFS and OS.
RESULTS: The SLR identified 16 unique studies from 9,909 records. While a lack of studies reporting EFS precluded analysis, 11 studies reporting DRFS, as the time from surgery to distant recurrence or death from any cause, were included. 10 of the 11 studies lacked a control arm, preventing trial-level surrogacy analysis. Among these 11 studies, arm-level 3-year DRFS and OS rates (73.5-93.4% and 86-100%, respectively) and 5-year rates (63.9-89.5%; 73.5-100%) were estimated. 10 studies had survival rates remaining above 50% by end of study follow-up, an indicator of the lack of data for longer-term survivors. Substantial heterogeneity in study characteristics (sample size, population characteristics, outcome definitions) was identified.
CONCLUSIONS: Limited evidence on EFS, DRFS, and OS outcomes among patients with high-risk, early-stage HR+/HER2- breast cancer in the neoadjuvant/adjuvant treatment setting challenges the ability to accurately quantify the surrogacy relationship between EFS or DRFS with OS. Additional clinical data are needed.
METHODS: The systematic literature review (SLR) identified studies reporting EFS, DRFS, and OS in patients with HR+/HER2- breast cancer in the neoadjuvant/adjuvant treatment setting, focusing on neoadjuvant chemotherapy followed by surgery and adjuvant endocrine therapy (± adjuvant chemotherapy). Published real-world evidence and randomized controlled trials were assessed for suitability in the surrogacy outcome analysis, considering study design, population heterogeneity, endpoint definitions, and data maturity. Both trial-level and arm-level surrogacy were considered. Weighted linear regression analyses were planned based on landmark EFS/DRFS and OS rates to explore arm-level association between EFS/DRFS and OS.
RESULTS: The SLR identified 16 unique studies from 9,909 records. While a lack of studies reporting EFS precluded analysis, 11 studies reporting DRFS, as the time from surgery to distant recurrence or death from any cause, were included. 10 of the 11 studies lacked a control arm, preventing trial-level surrogacy analysis. Among these 11 studies, arm-level 3-year DRFS and OS rates (73.5-93.4% and 86-100%, respectively) and 5-year rates (63.9-89.5%; 73.5-100%) were estimated. 10 studies had survival rates remaining above 50% by end of study follow-up, an indicator of the lack of data for longer-term survivors. Substantial heterogeneity in study characteristics (sample size, population characteristics, outcome definitions) was identified.
CONCLUSIONS: Limited evidence on EFS, DRFS, and OS outcomes among patients with high-risk, early-stage HR+/HER2- breast cancer in the neoadjuvant/adjuvant treatment setting challenges the ability to accurately quantify the surrogacy relationship between EFS or DRFS with OS. Additional clinical data are needed.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO142
Topic
Clinical Outcomes
Topic Subcategory
Relating Intermediate to Long-term Outcomes
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Oncology