Platinum vs non-platinum chemotherapy for platinum-resistant ovarian cancer: A meta-analysis.

Abstract

e17551 Background: recurrent ovarian cancer (OC) patients with platinum-free interval (PFI) < 6 mo. are usually considered platinum-resistant and treated with non-platinum chemotherapy. However, this practice is not based on proper-conducted randomized trials. Methods: we queried the PubMed database for all full-text articles and abstracts on the treatment of patients with platinum-resistant ovarian cancer (PROC) in 01/01/2000-01/06/2019 timeframe. The PRISMA tool was used to ensure transparent reporting of the results. Inclusion criteria were: 1) histologically confirmed epithelial OC; 2) recurrent disease within 6 months after completion of platinum chemotherapy; 3) treatment with platinum- or non-platinum chemotherapy agents that are routinely used for OC; 4) no concomitant therapy with targeted or investigational agents; 5) defined response rate (RR) and assessment criteria. Proportion meta-analysis (random-effect model) and beta-regression were conducted to assess the impact of platinum agents on response rate as well as significance of other variables. In the beta-regression model response rate was a dependent variable, while platinum agents (yes or no), used non-platinum drugs and method of response assessment were independent variables. Statistical analysis was dose with meta and betareg packages of R software. Results: we identified 7156 articles and screened them for title and abstract, 157 studies for further analysis. Efficacy of non-platinum- and platinum-based therapy was assessed in 113 (n = 5272) and 44 (n = 1055) trials respectively. In meta-proportion random-effect model RR among patients treated with platinum-based and non-platinum chemotherapy RR was 36% (95% CI 30-41; I2 = 62%) and 16% (95% CI 14-19; I2= 70%) respectively. Multiple beta-regression model is presented in the Table below. For sensitivity analysis various regression models were made with different subsets of the trials and additional variables (including year of the trial, percentage of serous subtype of OC and median of prior therapy lines). Platinum was the strongest predictor of response in every developed model. Conclusions: this meta-analysis shows that patients with 'platinum-resistant' ovarian carcinoma may derive significant benefit from reintroduction of platinum agents. These results support recent ESMO-ESGO consensus on treatment of recurrent ovarian cancer and randomize trials are required to refine the role of platinum in early relapsed OC.[Table: see text]