Ovarian cancer is a common female malignant tumor with high morbidity and mortality, ranking third among gynecological malignant tumors. Approximately 70% of patients relapse within 3 years after completion of first-line chemotherapy, and the average 5-year survival rate of ovarian cancer is lower than that of other tumor types (1, 2). Although patients with ovarian cancer are significantly sensitive to platinum-based chemotherapy agents, many patients experience recurrence and disease progression within 3 years of treatment, highlighting the need for therapies that improve clinical outcomes. In about half of patients with serous ovarian cancer, the homologous recombination repair function of cancer cells is missing, resulting in double stranded DNA damage that cannot be repaired. Homologous recombination repair defects are usually caused by mutations in cancer suppressor genes BRCA1 and BRCA2, which inhibit polyadenyldiphosphate ribose polymerase with single strand DNA breaks mainly through base excision repair pathway, resulting in double strand breaks (3). Olaparib is a poly ADP ribose polymerase (PARP) inhibitor. It shows significant clinical activity in ovarian cancer, especially BRCA1 and BRCA2 mutant cancer. It can inhibit DNA single strand repair, lead to cancer cell apoptosis and improve the effect of chemotherapy. Olaparib has been approved as a maintenance treatment for platinum sensitive patients with recurrent ovarian cancer in the United States and Europe. As the first targeted drug for ovarian cancer, it was approved by China food and drug administration to be listed in China in September 2018 (4). Clinically, it is often used alone or combined with paclitaxel and other conventional drugs to treat ovarian cancer, which has a significant effect and improves the overall survival and clinical benefit rate of cancer patients. However, there is a lack of systematic evaluation of the efficacy and safety of the drug in the treatment of ovarian cancer. Therefore, this paper evaluates the efficacy and safety of Olaparib in the treatment of ovarian cancer by synthesizing the existing clinical trial system, in order to provide clinical evidence.

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to report our meta-analysis. We systematically searched domestic and foreign literatures on the treatment of recurrent platinum sensitive ovarian cancer and systematically evaluated the efficacy and safety of Olaparib in the treatment of ovarian cancer.

Among gynecological malignancies, the death rate of ovarian cancer is higher. In 2020, there were 55342 new cases of female ovarian cancer in China, with 37519 deaths, accounting for 67.8% (13). Clinically, platinum and paclitaxel are the first choice chemotherapy drugs for ovarian cancer patients, and they are sensitive to the initial chemotherapy regimen. However, ovarian cancer patients have a high probability of recurrence and death within 3 years. The loss of sensitivity of cancer cells to the cytotoxicity of antitumor drugs seriously restricts the efficacy of antitumor drugs, which is also the main reason for the failure of ovarian cancer treatment. In recent years, robotics has been widely used in cancer treatment, especially in minimally invasive surgery, which plays a good role in the prognosis of cancer patients. Many studies have highlighted its safety and further advantages in performing some of the most complex surgical procedures. Valerio Gallotta et al. (14, 15) confirmed that robotic aortic lymphadenectomy plays a good role in gynecological cancer, especially in ovarian cancer patients, robotic surgery can improve the prognosis of patients. Breast cancer susceptibility genes (BRCA) is an important DNA homologous repair gene, which plays a major role in the normal cell DNA repair mechanism. However, BRCA mutation can lead to homologous recombination defects and cause tumor recurrence. BRCA has also become one of the main factors for risk assessment and prognosis of ovarian cancer in recent years (16). The BRCA gene has been shown to be a good predictor of ovarian cancer prognosis. Claudia Marchetti et al. (17) and Daniela Rivera et al. (18) showed that the IMPLEMENTATION of NGS based BRCA tumor tissue detection in FFPE ovarian cancer specimens confirmed that BRCA gene could predict the prognosis of patients. Genetic testing can be developed for patients through collaboration between pathology and genetics.

Olaparib is a potent oral poly (ADP-ribose) polymerase inhibitor that also acts against BRCA1 or BRCA2 mutations. In numerous clinical trials, olaparib therapy has shown significant antitumor activity in ovarian cancer patients with and without BRCA mutations. In platinum-sensitive recurrent serous ovarian cancer, maintenance treatment with olaparib significantly improved progression-free survival compared with the control group (hazard ratio [HR] 0.35 [95%CI 0.25-0.49]; p<0.0001), the greatest clinical benefit was recorded in patients with BRCA mutations (HR 0.18 [95%CI 0.10-0.31]; p<0.0001) (13). Preclinical data show that Olaparib may enhance the efficacy of DNA damage chemotherapy, including platinum containing drugs such as carboplatin. Carboplatin combined with paclitaxel is widely used in the treatment of platinum sensitive, recurrent and high-grade serous ovarian cancer. Many studies have shown that olaparib combined with chemotherapy has a significant effect in the treatment of advanced ovarian, breast and other solid tumors.

The results showed that the adverse reactions of olaparib group at all levels and above were higher than those of the control group. These adverse reactions mainly included nausea, fatigue, vomiting, diarrhea, abdominal pain and headache. Our subgroup analysis showed that except for abdominal pain, headache and vomiting, other adverse reactions were statistically significant. The above suggests that although olaparib can prolong the overall survival of patients in the clinical treatment of ovarian cancer, the adverse reactions similar to the above should not be ignored, especially the clinical symptoms such as nausea, fatigue and vomiting. If they are aggravated, they should be treated symptomatically in time, which will help to improve the discomfort and compliance of patients during medication.

In conclusion, the analysis of 6 clinical trials shows that olaparib is an ideal drug regimen for the treatment of recurrent platinum sensitive ovarian cancer, and its overall survival time is longer than that of the control group, but its incidence of adverse reactions is high, which should be paid attention to in clinical use. This study still needs to carry out more large sample and multi center RCTs to further provide basis for clinical medication.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

We declare that all authors made fundamental contributions to the manuscript. All authors contributed to the study conception and design. Database search and data analysis was conducted by QC and XL. Study selection and data extraction were performed by XL and ZZ. The manuscript was written by QC. TW reviewed the manuscript. All authors read and approved the final manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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