Evaluation of the Use of Surrogate Outcomes in Oncology Clinical Trials
Author(s)
Sharma R1, Goulding R2, Franklin M3
1Valuecom Evidence Based Solutions, Chandigarh, CH, India, 2Goulding HEOR, Inc, Vancouver, BC, Canada, 3Franklin Pharmaceutical Consulting, LLC, Rock Hill, SC, USA
Presentation Documents
Background: Overall survival (OS) is considered the gold standard efficacy measure in oncology clinical trials. Over the last decade other outcomes such as progression-free survival (PFS) and overall response rates (ORR), have been recognized by the FDA as efficacy surrogate markers, but use of surrogate outcomes may not be generalizable or appropriate across all cancer types. The purpose of this analysis was to identify and quantify the frequency and trends of surrogate outcomes across oncology clinical trials. Methods: A search was conducted in ClinicalTrials.gov from 01 January, 2017 - 31 October, 2021. Phase II/III or III interventional trials reporting solid tumor and blood cancer (adults) treatment efficacy endpoints were included. Information collected included cancer type, line of therapy, setting and primary efficacy endpoint(s). Frequency of OS versus surrogate endpoints was assessed according to cancer type, line of therapy, cancer progression rate and disease setting. Results: A total of 894 Phase II/III or III trials reporting efficacy endpoints were included, of which up to 80% were in solid tumors. OS was listed as a primary endpoint in 32% of included trials, of which approximately 50% listed OS with a surrogate endpoint. Most trials (83%) listed a surrogate primary endpoint, of which PFS was the most frequently used (58%). Evolving surrogate primary endpoints (reported in ≤10% trials) included disease-free/relapse-free survival, event-free survival (EFS), ORR, pathologic complete remission, metastasis-free survival, minimal residual disease negativity, and patient reported outcomes. Evolving endpoints were more frequently used for locally-advanced disease, whereas generally accepted surrogate endpoints such as PFS and ORR were more often used in advanced/metastatic settings and slow progressing cancers. Conclusions: Compared to OS, surrogate primary efficacy endpoints are frequently used in phase II/III or III oncology clinical trials. Evolving surrogate endpoints are often used in less advanced disease settings.
Conference/Value in Health Info
2022-05, ISPOR 2022, Washington, DC, USA
Value in Health, Volume 25, Issue 6, S1 (June 2022)
Code
CO155
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment, Relating Intermediate to Long-term Outcomes
Disease
No Additional Disease & Conditions/Specialized Treatment Areas