Improving the Clinical Meaning of Surrogate Endpoints: An Empirical Assessment of Clinical Progression in Phase III Oncology Trials

Authors

Alexander D Sherry
Timothy A Lin
Zachary R McCaw
Esther J Beck
Ramez Kouzy
Joseph Abi Jaoude
Adina H Passy
Avital M Miller
Gabrielle S Kupferman
Clifton David Fuller
Charles R Thomas
Eugene J Koay
Chad Tang
Pavlos Msaouel
Ethan B Ludmir

Publication Date

12-1-2024

Journal

International Journal of Cancer

DOI

10.1002/ijc.35129

PMID

39138841

PMCID

PMC11449668

PubMedCentral® Posted Date

12-1-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Disease progression in clinical trials is commonly defined by radiologic measures. However, clinical progression may be more meaningful to patients, may occur even when radiologic criteria for progression are not met, and often requires a change in therapy in clinical practice. The objective of this study was to determine the utilization of clinical progression criteria within progression-based trial endpoints among phase III trials testing systemic therapies for metastatic solid tumors. The primary manuscripts and protocols of phase III trials were reviewed for whether clinical events, such as refractory pain, tumor bleeding, or neurologic compromise, could constitute a progression event. Univariable logistic regression computed odds ratios (OR) and 95% CI for associations between trial-level covariates and clinical progression. A total of 216 trials enrolling 148,190 patients were included, with publication dates from 2006 through 2020. A major change in clinical status was included in the progression criteria of 13% of trials (n = 27), most commonly as a secondary endpoint (n = 22). Only 59% of trials (n = 16) reported distinct clinical progression outcomes that constituted the composite surrogate endpoint. Compared with other disease sites, genitourinary trials were more likely to include clinical progression definitions (16/33 [48%] vs. 11/183 [6%]; OR, 14.72; 95% CI, 5.99 to 37.84; p <  .0001). While major tumor-related clinical events were seldom considered as disease progression events, increased attention to clinical progression may improve the meaningfulness and clinical applicability of surrogate endpoints for patients with metastatic solid tumors.

Keywords

Humans, Disease Progression, Neoplasms, Clinical Trials, Phase III as Topic, Endpoint Determination, phase III: randomized controlled trials, clinical progression, quality of life, surrogate endpoints

Published Open-Access

yes

Recommended Citation

Sherry, Alexander D; Lin, Timothy A; McCaw, Zachary R; et al., "Improving the Clinical Meaning of Surrogate Endpoints: An Empirical Assessment of Clinical Progression in Phase III Oncology Trials" (2024). Faculty, Staff and Student Publications. 5672.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5672