Off study utilization of an unpublished trial regimen: A real-world analysis of GOG258-eligible cohorts.

Abstract

e18763 Background: Practice patterns in the management of advanced endometrial cancer are widely variable and treatment paradigms are rapidly changing given the evolving clinical trial landscape. Prior studies have demonstrated “medical reversals” where clinicians favor or utilize the experimental approach only to find inferiority on publication of results. The objective of this study was to examine the utilization of the GOG 258 arms-- (adjuvant chemotherapy (CT) vs chemoradiotherapy (CRT)-- for patients with advanced or high-risk endometrial cancer. Methods: Patients 18 years or older who underwent staging surgery with stage III/IVA endometrial carcinoma of any histology or stage I/II clear cell or serous histologies with positive washings diagnosed between 2004 and 2018 were identified in the National Cancer Database. Utilization of adjuvant CT and CRT were examined in the pre-GOG 258 era (before 2009), during GOG 258 enrollment (2010-2017), and after publication of results (2018). Two-sided Cochrane-Armitage test assessed trends over time. T-test and chi-square tests assessed differences in groups receiving CT alone vs CRT. Multivariable logistic regression assessed factors associated with receipt of CRT. Propensity score matching accounted for baseline differences in groups receiving CT vs CRT. Results: 40,028 patients were included. 16,342 (41%) received adjuvant CT and 23,686 (59%) received adjuvant CRT. The majority of patients (39,185, 98%) were advanced stage and 19,616 (49%) were endometrioid histology. 90% of patients receiving both CT and CRT received multiagent therapy. Utilization of CRT was 54% before GOG 258 opening, 60% during GOG 258 enrollment, and 67% after publication of results (p < 0.001). Factors associated with receipt of CT alone were age greater than 70 (adjusted odds ratio [aOR] 0.68, 95% confidence interval [CI] 0.46-0.99), non-Hispanic Black race (aOR 0.84, CI 0.77-0.92), serous and clear cell histologies (aOR 0.68, CI 0.59-0.77; aOR 0.74, CI 0.57-0.95), living greater than 50 miles from treatment facility (aOR 0.84, CI 0.77-0.92), and receiving care in the Midwest, South, and West regions (aOR 0.84, CI 0.78-0.90; aOR 0.69, CI 0.64-0.76; aOR 0.72, CI 0.66-0.78). Compared to an academic medical center, receiving care at a comprehensive community cancer center was associated with receipt of CRT (aOR 1.2, CI 1.2-1.3). Compared to pre-GOG 258 opening in 2009, patients were more likely to receive CRT during GOG 258 enrollment (aOR 1.2, CI 1.1-1.3) and immediately after results announcement in 2018 (aOR 1.7, CI 1.5-1.8), despite results showing that CRT was not associated with longer relapse-free or overall survival. Conclusions: For patients with advanced endometrial cancer, there was significant use of both study arms with increases in CRT use during the study enrollment period and immediately after reporting of GOG 258 results, despite lack of benefit in the CRT arm.