Takehiro Hirai1,2, Asuka Nemoto1, Yoshinori Ito3, Masaaki Matsuura4,5. 1. Teikyo University Graduate School of Public Health, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan. 2. Clinical Development Department, Daiichi Sankyo RD Novare Co., Ltd., Tokyo, Japan. 3. Breast Medical Oncology, Breast Oncology Center, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan. 4. Teikyo University Graduate School of Public Health, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan. mmatsuura@med.teikyo-u.ac.jp. 5. Division of Cancer Genomics, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan. mmatsuura@med.teikyo-u.ac.jp.
Abstract
PURPOSE: Earlier studies suggest progression-free survival (PFS) may be used as a surrogate endpoint for overall survival (OS) in metastatic breast cancer, which could shorten follow-up duration and speed up assessment of treatment effects. However, to our knowledge, the association between them is still unclear in advanced or metastatic triple-negative breast cancer (TNBC). METHODS: A literature-based meta-analysis followed by correlation analysis was conducted in advanced or metastatic TNBC. Weighted multiple regression analysis was then used to test the strength of the association between medians of PFS and OS, and the association between HRPFS and HROS. RESULTS: Fourteen randomized clinical trials published between January 2007 and August 2019, 31 median pairs for PFS and OS, and 17 pairs for HRPFS and HROS from 3,880 patients were selected. The Pearson correlation coefficient between medians of PFS and OS was 0.84 (95% confidence interval (CI) 0.68-0.92, p < 0.001), and the correlation coefficient between HRPFS and HROS was 0.86 (95% CI 0.63-0.95, p < 0.001). Weighted multiple regression analysis showed HRPFS was the most significant predictor of HROS among covariates analyzed (p < 0.001). Both the medians of PFS and OS correlation, and the HRPFS and HROS correlation were 0.79 (p < 0.001), 0.80 (p = 0.001), respectively, in the 11 trials excluding immunotherapy and bevacizumab-based therapy trials. CONCLUSIONS: Our analysis suggests PFS can be strongly correlated with OS and considered a valid surrogate endpoint for OS in advanced or metastatic TNBC.
PURPOSE: Earlier studies suggest progression-free survival (PFS) may be used as a surrogate endpoint for overall survival (OS) in metastatic breast cancer, which could shorten follow-up duration and speed up assessment of treatment effects. However, to our knowledge, the association between them is still unclear in advanced or metastatic triple-negative breast cancer (TNBC). METHODS: A literature-based meta-analysis followed by correlation analysis was conducted in advanced or metastatic TNBC. Weighted multiple regression analysis was then used to test the strength of the association between medians of PFS and OS, and the association between HRPFS and HROS. RESULTS: Fourteen randomized clinical trials published between January 2007 and August 2019, 31 median pairs for PFS and OS, and 17 pairs for HRPFS and HROS from 3,880 patients were selected. The Pearson correlation coefficient between medians of PFS and OS was 0.84 (95% confidence interval (CI) 0.68-0.92, p < 0.001), and the correlation coefficient between HRPFS and HROS was 0.86 (95% CI 0.63-0.95, p < 0.001). Weighted multiple regression analysis showed HRPFS was the most significant predictor of HROS among covariates analyzed (p < 0.001). Both the medians of PFS and OS correlation, and the HRPFS and HROS correlation were 0.79 (p < 0.001), 0.80 (p = 0.001), respectively, in the 11 trials excluding immunotherapy and bevacizumab-based therapy trials. CONCLUSIONS: Our analysis suggests PFS can be strongly correlated with OS and considered a valid surrogate endpoint for OS in advanced or metastatic TNBC.
Entities:
Keywords:
Meta-analysis; Overall survival; Progression-free survival; Surrogate endpoint; Triple-negative breast cancer