Utilization of Overall Survival and Other Survival Endpoints in Clinical Trials for Adjuvant Therapies in Resectable Tumors
Author(s)
Krzysztof Kloc, MSc1, Imen Reguei, MSc2, Zeineb Hammami, MSc2, Mariem El Haj, MSc2, Mondher Toumi, PhD3.
1Clever-Access, Krakow, Poland, 2Clever-Access, Tunis, Tunisia, 3Inovintell, Krakow, Poland.
1Clever-Access, Krakow, Poland, 2Clever-Access, Tunis, Tunisia, 3Inovintell, Krakow, Poland.
OBJECTIVES: Recurrence is a common endpoint for resectable tumour trials while overall survival (OS) is the payers’ preferred outcome, especially for curative therapies despite requiring longer follow-ups. The analysis aimed to describe the endpoints in industry-funded trials in an adjuvant setting, focusing on the utilization of OS, progression-free survival (PFS), event-free-survival (EFS), disease-free survival (DFS) and quality of life (QoL).
METHODS: Interventional, Phase 3, industry-funded trials in adjuvant settings were identified and extracted from clinicaltrials.gov, and restricted to oncology trials concerning curative therapies or resectable tumours.
RESULTS: A total of 257 trials were identified, which included adjuvant treatments and focused on resectable tumours or evaluated therapies with curative intent. OS and PFS were not frequently used as primary or co-primary endpoints in those trials (6% and 4%, respectively). The majority of trials (61%) adopted EFS/DFS as (co-)primary endpoints, followed by recurrence or response rates (13% and 11% of trials, respectively). However, OS was included as a secondary endpoint in 82% of trials involving resectable tumours. In studies that used EFS/DFS as (co-)primary endpoints, OS was employed as a secondary endpoint in 95%of cases. The mean follow-up of OS in all resectable cancer trials was 300 weeks (range: 45 weeks to 20.5 years), while when OS was the (co-)primary outcome, it was 268 weeks. Only 39.7% of studies included QoL secondary endpoints.
CONCLUSIONS: EFS/DFS are key measures in resectable tumours and are mainly driven by disease recurrence. OS is considered in most studies but as a secondary outcome, likely to be immature and underpowered at the time of approval. Evidence indicates that breakthrough therapy and early access programs do not hold promises. To mitigate payers’ resistance, coverage with evidence development and escrow agreements should be established until OS is reached. The validation of surrogate EFS/DFS endpoints should also be considered early in the development.
METHODS: Interventional, Phase 3, industry-funded trials in adjuvant settings were identified and extracted from clinicaltrials.gov, and restricted to oncology trials concerning curative therapies or resectable tumours.
RESULTS: A total of 257 trials were identified, which included adjuvant treatments and focused on resectable tumours or evaluated therapies with curative intent. OS and PFS were not frequently used as primary or co-primary endpoints in those trials (6% and 4%, respectively). The majority of trials (61%) adopted EFS/DFS as (co-)primary endpoints, followed by recurrence or response rates (13% and 11% of trials, respectively). However, OS was included as a secondary endpoint in 82% of trials involving resectable tumours. In studies that used EFS/DFS as (co-)primary endpoints, OS was employed as a secondary endpoint in 95%of cases. The mean follow-up of OS in all resectable cancer trials was 300 weeks (range: 45 weeks to 20.5 years), while when OS was the (co-)primary outcome, it was 268 weeks. Only 39.7% of studies included QoL secondary endpoints.
CONCLUSIONS: EFS/DFS are key measures in resectable tumours and are mainly driven by disease recurrence. OS is considered in most studies but as a secondary outcome, likely to be immature and underpowered at the time of approval. Evidence indicates that breakthrough therapy and early access programs do not hold promises. To mitigate payers’ resistance, coverage with evidence development and escrow agreements should be established until OS is reached. The validation of surrogate EFS/DFS endpoints should also be considered early in the development.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO182
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment, Relating Intermediate to Long-term Outcomes
Disease
SDC: Oncology