Efficacy and Safety of Adavosertib in Platinum-Resistant and RecurrentOvarian Cancer: A Systematic Review and A Meta-Analysis

Abstract

Introduction: Ovarian cancer is a leading cause of mortality among gynaecological malignancies. According to estimates from the American Cancer Society for 2024, approximately 19,680 women in the United States will be newly diagnosed with ovarian cancer, and about 12,740 women will succumb to the disease. Advanced-stage ovarian cancers frequently develop resistance to treatment, resulting in a poor overall prognosis for this patient population. This article presents a systematic review and meta-analysis examining the efficacy and safety profile of adavosertib in treating platinum-resistant or recurrent ovarian cancers.

Methodology: The research question was framed using the PICO framework before initiating the review. A comprehensive literature search was conducted across PubMed, Google Scholar, Scopus, HINARI, and ScienceDirect databases, covering publications up to August 2023. Inclusion and exclusion criteria were defined, and appropriate tools were utilized to assess the risk of bias in the included studies. Descriptive and summary statistics were employed to characterize the sociodemographic features of the study cohort and the adverse effects associated with adavosertib. A random-effects model meta-analysis was performed to evaluate the association between adavosertib and the overall median survival of patients.

Results: In the meta-analysis using a random-effects model, the pooled estimate for the overall survival of patients given adavosertib is 14.71 months (95%CI: 9.01 to 20.41 months). The estimate is statistically significant (p < 0.0001), indicating a positive effect of adavosertib on overall survival. The amount of total heterogeneity (variability between studies) is estimated to be 18.97 (SE = 26.19), with a corresponding tau value of 4.35. The I² statistic is 77.36%, indicating a high level of heterogeneity among the studies. The most common adverse effects were nausea (69.3%), anemia (60.3%), diarrhea (56.8%), thrombocytopenia (55.0%), neutropenia (54%), vomiting (52.7%), lymphopenia (35.6%), hypomagnesemia (9.0%), and hypokalemia (5.4%).

Conclusion: The meta-analysis suggests that adavosertib has a significant positive effect on overall survival in ovarian cancer patients, with an estimated pooled median survival of 14.71 months. However, the results should be interpreted cautiously due to the high heterogeneity observed among the studies. The top three most common adverse effects were nausea, anemia, and diarrhea. Larger studies are recommended to provide more comprehensive information on this topic.