Abstract 4007: Decipher the myth between progression-free survival and overall survival in HER-2 positive metastatic nreast cancer: Anti-HER2 antibody as the constant winner—A hypothesis-driven meta-regression analysis

Abstract

Abstract Purpose: Traditionally, the predictive value of progression free survival (PFS) hazard ratio (HR) on overall survival (OS) HR in metastatic breast cancer (MBC) was low. We observed that when trials were designed as adding on an anti-HER2 antibody, either trastuzumab or pertuzumab, to the control treatment, the OS increment is usually greater than the PFS increment. We aim to investigate the interaction of increment of median PFS and median OS in HER-2 positive MBC stratified by drug difference patterns between treatment arms using trial-level information. Methods: All randomized phase II or III trials of systematic therapy specifically for HER-2 positive MBC with available OS information were included after a systematic literature review. Treatment arms with shorter PFS were defined as control arm in the analysis. The correlation and interaction of HR for PFS and OS as well as the absolute increment for median PFS and OS were evaluated by fixed-effect or random-effect meta-regression meta-analysis. Drug difference between two treatment arms were specified as a categorical variable in the analysis. Results: A total of 28 trials with 10928 patients published between January 1999 and December 2017 were included in the final analysis. The correlation of median PFS HR (0.73, 95% C.I.= 0.68-078) and median OS HR (0.82, 95% C.I.= 0.77-0.87) was modest as reported by other investigators. However, when the drug difference between treatment arms was anti-HER2 antibody, the absolute increment in median OS is 2 fold of the absolute increment in median PFS (p = 0.0005), showing a linear correlation. This linear correlation was not observed when the drug difference between treatments was non-anti-HER2 antibody. Anti-HER2 antibody as drug difference would translate the absolute increment of median PFS into absolute increment of median OS, suggesting a good predictive value of median PFS on median OS. Conclusion: Anti-HER2 antibody as the drug difference between treatment arms provides consistently longer OS improvement than PFS improvement in HER-2 positive MBCs. Citation Format: I-Chun Chen, Fu-Chiang Hu, Ching-Hung Lin, Yen-Shen Lu. Decipher the myth between progression-free survival and overall survival in HER-2 positive metastatic nreast cancer: Anti-HER2 antibody as the constant winner—A hypothesis-driven meta-regression analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4007.