Surrogate endpoints in platinum-resistant recurrent ovarian cancer
Background: overall survival (OS) is the gold-standard primary end point for cancer clinical trials to evaluate the outcome of therapy. However, in some cases the direct assessment of OS can be inappropriate. Therefore, various surrogate endpoints, such as overall response rate (ORR) and progression-free survival (PFS), are used commonly in clinical trials. Aim: to assess the relevance of mentioned endpoints in platinum-resistant recurrent ovarian cancer. Patients and Methods: we used PubMed queries to search for all ovarian cancer studies from 01/01/2000 to 07/01/2019. Key inclusion criteria were: 1) recurrent epithelial ovarian cancer, 2) platinum-free interval ≤6 months, 3) standard chemotherapy (CT) without targeted and/or experimental drugs, 4) reported objective response rate, PFS and OS, as well as response assessment criteria. Correlation and linear regression analysis were conducted to identify the relationship between various markers of therapy efficacy. Trials were weighted according to the number of enrolled patients. Statistical analysis of the data was performed using R and RStudio software. Results: 7156 studies were reviewed, and 157 studies meeting the inclusion/exclusion criteria were selected. PFS and OS data were available in 104 (n=5081) and 99 (n=5089) studies, respectively. The average ORR was 17.2% (non-platinum CT - 13.6%, platinum-based CT - 36.7%; p<0.001), and median PFS was 3.68 months (3.38 and 5.37 months, respectively; p<0.001). A significant correlation was found between ORR and PFS (r=0.62; p<0.001). Linear regression analysis identified 0.5 months increase in median PFS for every 10% increase in ORR (p<0.001). There was no significant correlation between ORR and OS. Conclusions: the meta-analysis results provide valuable information for understanding the role of surrogate biomarkers in platinum-resistant recurrent ovarian cancer. ORR is a reliable predictor of PFS in this patient population.