Earlier time-to-event (TTE) endpoints than overall survival (OS) will allow more timely regulatory approval and overall accelerated drug development. Thus, in this post hoc analysis, the authors aimed to estimate correlations between TTE endpoints such as rPFS, time to first SSE, and OS and provide further evidence for rPFS as an early endpoint for regulatory approval, in the context of radioligand therapy (RLT).
The authors calculated Spearman’s rank correlations between rPFS, OS and time to first SSE using three methods adapted to TTE endpoints as censoring prevented observation of events. Correlation estimations were used for both VISION protocol data (as is) and imputed data. For the latter, imputation methods were used for rPFS and OS to adjust for informative censoring; for time to first SSE, patients were censored 30 days after first treatment change or death.
Results of the three different approaches to calculate Spearman’s rank correlation provided comparable results. The correlation between rPFS and OS was moderate-to-strong using both protocol and imputed data, with estimates of ∼0.7 or higher.
Stronger associations between rPFS/OS and SSE were observed for protocol vs. imputed data; however, SSE data mainly contained information on OS for the protocol data.
Dr. Morris concluded that, in this first analysis performed in the context of radioligand therapy, there was a moderate-to-strong correlation between rPFS and OS. Thus, rPFS, as defined by PCWG3, may be relevant as an early endpoint for regulatory approval and clinical trial design in this context.
Presented by: Michael Morris, MD, Medical Oncologist Clinical Director, Genitourinary Medical Oncology Service & Prostate Cancer Section Head, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2022 European Society of Medical Oncology (ESMO) Annual Hybrid Meeting, Paris, FR, Fri, Sept 9 – Tues, Sept 13, 2022.