Proportion of patients in phase I solid tumor oncology trials receiving treatments that are clinically efficacious.
Authors: Muzlera Carlos Umberto , Elimova Elena 
Published: June 2023

6582 Retraction The abstract by Muzlera and Elimova entitled, “Proportion of patients in phase I solid tumor oncology trials receiving treatments that are clinically efficacious,” ( Journal of Clinical Oncology 41, no. 16_suppl 6582; DOI 10.1200/JCO.2023.41.16_suppl.6582) published on May 31, 2023, has been retracted by the authors due to statistical errors that have significantly changed the results and conclusion of the abstract. This abstract has been retracted as of August 9, 2024. Background: Phase I trials are frequently regarded as possessing therapeutic intent by patients, oncologists, and governing medical bodies alike. While obtaining initial observations of clinical activity of investigational agents is an aim of phase I trials, such estimates utilize surrogate measures, such as objective response rate, which are difficult to conceptualize and less meaningful to a vulnerable patient population compared to clinical endpoints. Furthermore, phase I studies lack a comparator arm. To date, there are no published estimates of the probability a phase I solid tumor participant receives a treatment at a dose that has greater clinical efficacy than the standard of care for their disease setting. Such data is required to enable fully informed decisions around consent. Methods: A random sample of 1000 phase I solid tumor oncology trials conducted world-wide, initiated between 2007 and 2012, and enrolling 29,953 patients was obtained from 2223 eligible trials on ClinicalTrials.gov. ClinicalTrials.gov, PubMed, Embase, Medline, and ASCO reports were queried between December 1, 2022 and February 1, 2023 for randomized, controlled phase III trials testing the same regimen and indication as that used in each phase I trial. Phase III trials were considered positive if they demonstrated statistically significant superiority over an acceptable standard of care at the time of enrolment of the corresponding phase I trial with respect to overall survival, health related quality of life, or a validated surrogate for these clinical endpoints. All statistical tests were 2-sided. Results: A total of 0.82% (245) phase I trial patients received a treatment at a dose that was subsequently demonstrated in a randomized, controlled phase III trial to have statistically superior clinical efficacy over an acceptable standard of care at the time of phase I trial enrolment for the same disease setting. The mean objective response rate for both published and unpublished sampled phase I trials in the advanced or metastatic setting was 4.2%. Meta-regression showed a statistically significantly greater proportion of patients receiving a clinically efficacious therapy in biomarker trials (rate ratio = 3.78., 95% CI = 1.15 – 10.24, P = 0.02) and trials with an expansion cohort (rate ratio = 3.12, 95% CI = 1.05 – 8.89, P = 0.03). Proportions were statistically significantly lower for first in class treatments (rate ratio = 0.21, 95% CI = 0.03 – 0.76, P = 0.03). Conclusions: One in 122 patients in phase I solid tumor trials received a treatment that subsequently demonstrated superior clinical efficacy over the standard of care at the time of phase I trial enrolment. Considering published estimates of serious adverse events rates of 10-19%, this reveals low therapeutic value for phase I trial participation.