Verification of the Correlation between Progression-free Survival and Overall Survival Considering Magnitudes of Survival Postprogression in the Treatment of Four Types of Cancer

摘要

Background: With development and application of new and effective anti-cancer drugs, the median survivalpost-progression (SPP) is often prolonged, and the role of the median SPP on surrogacy performance shouldbe considered. To evaluate the impact of the median SPP on the correlation between progression-free survival(PFS) and overall survival (OS), we performed simulations for treatment of four types of cancer, advancedgastric cancer (AGC), metastatic colorectal cancer (MCC), glioblastoma (GBM), and advanced non-small-celllung cancer (ANSCLC). Materials and Methods: The effects of the median SPP on the statistical propertiesof OS and the correlation between PFS and OS were assessed. Further, comparisons were made between thesurrogacy performance based on real data from meta-analyses and simulation results with similar scenarios.Results: The probability of a significant gain in OS and HR for OS was decreased by an increase of the SPP/OS ratio or by a decrease of observed treatment benefit for PFS. Similarly, for each of the four types of cancer,the correlation between PFS and OS was reduced as the median SPP increased from 2 to 12 months. Except forANSCLC, for which the median SPP was equal to the true value, the simulated correlation between PFS and OSwas consistent with the values derived from meta-analyses for the other three kinds of cancer. Further, for thesethree types of cancer, when the median SPP was controlled at a designated level (i.e., < 4 months for AGC, < 12months for MCC, and <6 months for GBM), the correlation between PFS and OS was strong; and the powerof OS reached 34.9% at the minimum. Conclusions: PFS is an acceptable surrogate endpoint for OS under thecondition of controlling SPPs for AGC, MCC, and GBM at their limit levels; a similar conclusion cannot bemade for ANSCLC.