Optimizing disease progression assessment using blinded central independent review and comparing it with investigator assessment in the PRIMA/ENGOT-ov26/GOG-3012 trial: challenges and solutions.

Abstract

OBJECTIVE:

Progression-free survival is an established clinically meaningful endpoint in ovarian cancer trials, but it may be susceptible to bias; therefore, blinded independent centralized radiological review is often included in trial designs. We compared blinded independent centralized review and investigator-assessed progressive disease performance in the PRIMA/ENGOT-ov26/GOG-3012 trial examining niraparib monotherapy.

METHODS:

PRIMA/ENGOT-ov26/GOG-3012 was a randomized, double-blind phase 3 trial; patients with newly diagnosed stage III/IV ovarian cancer received niraparib or placebo. The primary endpoint was progression-free survival (per Response Evaluation Criteria in Solid Tumors [RECIST] v1.1), determined by two independent radiologists, an arbiter if required, and by blinded central clinician review. Discordance rates between blinded independent centralized review and investigator assessment of progressive disease and non-progressive disease were routinely assessed. To optimize disease assessment, a training intervention was developed for blinded independent centralized radiological reviewers, and RECIST refresher training was provided for investigators. Discordance rates were determined post-intervention.

RESULTS:

There was a 39% discordance rate between blinded independent centralized review and investigator-assessed progressive disease/non-progressive disease in an initial patient subset (n=80); peritoneal carcinomatosis was the most common source of discordance. All reviewers underwent training, and as a result, changes were implemented, including removal of two original reviewers and identification of 10 best practices for reading imaging data. Post-hoc analysis indicated final discordance rates between blinded independent centralized review and investigator improved to 12% in the overall population. Median progression-free survival and hazard ratios were similar between blinded independent centralized review and investigators in the overall population and across subgroups.

CONCLUSION:

PRIMA/ENGOT-ov26/GOG-3012 highlights the need to optimize blinded independent centralized review and investigator concordance using early, specialized, ovarian-cancer-specific radiology training to maximize validity of outcome data.

• Authors: Thomas J Herzog, Shaun A Wahab, Mansoor R Mirza, Bhavana Pothuri, Ignace Vergote, Whitney S Graybill, Izabela A Malinowska, Whitney York, Jean A Hurteau, Divya Gupta, Antonio González-Martin, Bradley J Monk
• Journal: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society (Int J Gynecol Cancer) Vol. 33 Issue 11 Pg. 1733-1742 (11 06 2023) ISSN: 1525-1438 [Electronic] England
• PMID: 37931976 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.

Topics

• Female
• Humans
• Carcinoma, Ovarian Epithelial (drug therapy)
• Disease Progression
• Ovarian Neoplasms (pathology)
• Peritoneal Neoplasms (pathology)
• Progression-Free Survival
• Randomized Controlled Trials as Topic
• Clinical Trials, Phase III as Topic