Association Between Invasive Disease-Free Survival/Distant Recurrence-Free Survival and Overall Survival in Patients With Early Stage Triple-Negative Breast Cancer
Author(s)
Aurelien Jamotte, MSc1, Amin Haiderali, MBA, MPH2, Jagadeswara Rao Earla, MBA, PharmD, PhD3, Ketsia Habimana, MSc4, Jane Candlish, PhD4, Amit Ahuja, M.Pharm5, Sakshi Jindal, M.Pharm5, Kanupriya Mahajan, M.Pharm5, Aniket Sharma, M.Pharm5, Ioana Gulas, MSc6, Tracy Westley, MSPH7, Peter Fasching, Prof., MD8.
1Principal Scientist, Health Economics & Decision Sciences, MSD Innovation & Development GmbH, Zurich, Switzerland, 2Merck & Co., Inc., Rahway, NJ, USA, 3Merck & Co. Inc, Rahway, NJ, USA, 4Lumanity, Sheffield, United Kingdom, 5Lumanity, Gurugram, India, 6Lumanity, Toronto, ON, Canada, 7Lumanity, Bethesda, MD, USA, 8University Hospital Erlangen, Erlangen, Germany.
1Principal Scientist, Health Economics & Decision Sciences, MSD Innovation & Development GmbH, Zurich, Switzerland, 2Merck & Co., Inc., Rahway, NJ, USA, 3Merck & Co. Inc, Rahway, NJ, USA, 4Lumanity, Sheffield, United Kingdom, 5Lumanity, Gurugram, India, 6Lumanity, Toronto, ON, Canada, 7Lumanity, Bethesda, MD, USA, 8University Hospital Erlangen, Erlangen, Germany.
OBJECTIVES: Validating surrogate endpoints can support earlier evaluation of new treatments, accelerate regulatory approvals and support health technology assessments. We aimed to quantify the surrogate relationship between invasive disease-free survival (IDFS) or distant recurrence-free survival (DRFS) with overall survival (OS) in patients with early-stage triple-negative breast cancer (TNBC) in the adjuvant treatment setting.
METHODS: A systematic literature review (SLR) identified studies reporting IDFS, DRFS or comparable outcomes with OS. Comparable published real-world evidence and randomized controlled trials were determined by treatment setting, population characteristics, endpoint definitions, and endpoint data maturity. Trial- and arm-level (cohort) surrogacy analyses were planned to use weighted linear regression models for hazard ratios (HRs) and landmark survival rates to study the relationship between IDFS/IDRFS and OS.
RESULTS: The SLR identified 13 unique studies from 9,909 records, and 3 studies were subsequently excluded from the surrogacy analyses due to a lack of relevant data reported. 10 studies reported IDFS or equivalent endpoints, while no study reported DRFS. A lack of controlled studies prevented trial-level analysis requiring HRs. Among the 10 studies, arm-level (landmark) IDFS rates ranged 41.9-86.7% at 3 years and 40.6-81.8% at 5 years, while OS rates ranged 55.5-91.1% at 3 years and 52.5-87.8% at 5 years. Moderate (0.7<ρ<0.85) to strong (ρ≥0.85) sample-weighted correlations were found for all analyses. 3-year IDFS rates strongly correlated with 3-year and 5-year OS rates, whereas 5-year IDFS rates moderately correlated with 5-year OS rates. However, substantial heterogeneity in study characteristics was observed, including sample size, population characteristics, and outcome definitions.
CONCLUSIONS: Limited evidence (none for DRFS) was found for patients with early-stage TNBC in the adjuvant setting to accurately quantify the surrogacy relationship between IDFS or DRFS to OS. Treatment-arm landmark survival rates analysis suggests IDFS as a potential surrogate for OS. Additional clinical data are needed in this setting.
METHODS: A systematic literature review (SLR) identified studies reporting IDFS, DRFS or comparable outcomes with OS. Comparable published real-world evidence and randomized controlled trials were determined by treatment setting, population characteristics, endpoint definitions, and endpoint data maturity. Trial- and arm-level (cohort) surrogacy analyses were planned to use weighted linear regression models for hazard ratios (HRs) and landmark survival rates to study the relationship between IDFS/IDRFS and OS.
RESULTS: The SLR identified 13 unique studies from 9,909 records, and 3 studies were subsequently excluded from the surrogacy analyses due to a lack of relevant data reported. 10 studies reported IDFS or equivalent endpoints, while no study reported DRFS. A lack of controlled studies prevented trial-level analysis requiring HRs. Among the 10 studies, arm-level (landmark) IDFS rates ranged 41.9-86.7% at 3 years and 40.6-81.8% at 5 years, while OS rates ranged 55.5-91.1% at 3 years and 52.5-87.8% at 5 years. Moderate (0.7<ρ<0.85) to strong (ρ≥0.85) sample-weighted correlations were found for all analyses. 3-year IDFS rates strongly correlated with 3-year and 5-year OS rates, whereas 5-year IDFS rates moderately correlated with 5-year OS rates. However, substantial heterogeneity in study characteristics was observed, including sample size, population characteristics, and outcome definitions.
CONCLUSIONS: Limited evidence (none for DRFS) was found for patients with early-stage TNBC in the adjuvant setting to accurately quantify the surrogacy relationship between IDFS or DRFS to OS. Treatment-arm landmark survival rates analysis suggests IDFS as a potential surrogate for OS. Additional clinical data are needed in this setting.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO21
Topic
Clinical Outcomes
Topic Subcategory
Relating Intermediate to Long-term Outcomes
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Oncology