@article{9f5766812ca04984900ce95c46e26598,
title = "Assessing surrogacy using restricted mean survival time ratio for overall survival in non-small cell lung cancer immunotherapy studies",
abstract = "Background: Background: Proportional hazards (PH) assumption is often violated in cancer immunotherapy studies. Restricted mean survival time (RMST) ratio is a valid metric to quantify the size of treatment effect when non-proportional hazard (NPH) is present. This study investigated the use of RMST ratio and hazard ratio (HR) in studying progression-free survival (PFS) as a surrogate endpoint for overall survival (OS) in non-small cell lung cancer immunotherapy trials. Methods: Trial level data were collected from 14 phase III trials published between 2012 and 2018. A weighted least-square regression (WLSR) was performed to evaluate the trial-level surrogacy. Surrogacy was evaluated via the association between RMST ratios for PFS and OS and between HRs for PFS and OS. Results: Using data extracted from published articles, low to moderate correlation (0.49) between PFS and OS was observed for HR while low correlation (0.35) was observed for RMST ratio. When trials violating PH in PFS were included, more consistent correlations for both HR (0.43) and RMST ratio (0.44) were observed. Conclusions: In summary, the strength of PFS surrogacy for OS depends on whether HR or RMST ratio are chosen. RMST ratio and additional sensitivity analysis should be considered in addition to HR.",
keywords = "Immunotherapy, lung cancer, progression-free survival (PFS), restricted mean survival time (RMST), surrogate endpoint",
author = "Herbert Pang and Guangyu Yang and Ho, {James C.} and Leung, {Tiffany H.} and Qian Shi and Chen Hu and Stinchcombe, {Thomas E.} and Xiaofei Wang",
note = "Funding Information: We would like to thank Liyuan Fan for her help with some of the data extraction. Funding: The research work was partially supported by NIH P01CA142538 (Wang) and NIH R01AG066883 (Wang), HMRF grant of Hong Kong 16172901 (Pang, Ho), University Postgraduate Fellowships of HKU Foundation (Leung) and Postgraduate scholarship of the University of Hong Kong (Leung). Funding Information: ICMJE uniform disclosure form (available at https://cco. amegroups.com/article/view/10.21037/cco-21-110/coif). HP reports HMRF grant of Hong Kong 16172901, an NIHU01 grant from FDA, stock options from Roche, and personal fees from Genentech, outside the submitted work. TL reports University Postgraduate Fellowships of HKU Foundation. QS reports consulting/advisory role from Yiviva Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Regeneron Pharmaceuticals, Inc., Hoosier Cancer Research Network (to QS), Honorarium/speaker role from Chugai Pharmaceutical Co., Ltd., stocks from Johnson & Johnson, Amgen, and Merck & CO. (to QS), research funds from Celgene/BMS, Roche/Genentech, Janssen, Novartis. CH reports support from NCI/NIH (U10-CA180822), grant from RTOG Foundation, and consulting fees from Merck & Co. and D1Med Technology Co. TES reports receiving grants or contracts from Genentech/Roche (Institution), AstraZeneca (Institution), Takeda (Institution), Advaxis (Institution), Regeneron (Institution), and Mirati (Institution); and participation on a Data Safety Monitoring Board or Advisory Board of Takeda, AstraZeneca, Genentech/Roche, Foundation Medicine, Pfizer, EMD Serono, Novartis, Daiichi Sankyo¸ Lilly, Medtronic, Puma Biotechnology, Janssen Oncology, Regeneron, Turning Point Therapeutics, Sanofi/Aventis. XW serves as an unpaid editorial board member of Chinese Clinical Oncology. The other authors have no conflicts of interest to declare. Publisher Copyright: {\textcopyright} Chinese Clinical Oncology. All rights reserved.",
year = "2022",
month = feb,
doi = "10.21037/cco-21-110",
language = "English (US)",
volume = "11",
journal = "Chinese clinical oncology",
issn = "2304-3865",
publisher = "Society for Translational Medicine (STM)",
number = "1",
}