Efficacy and safety of PARP inhibitors in elderly patients with advanced ovarian cancer: a systematic review and meta-analysis

Background Poly-(ADP-ribose)-polymerase (PARP) inhibitors have shown to be effective as maintenance treatment in patients with advanced ovarian cancer. Although most ovarian cancers develop after age 65, older patients are often under-represented in clinical trials. Objective To assess the efficacy and safety of PARP inhibitors versus placebo as maintenance therapy in older patients with ovarian cancer. Methods This systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items of Systematic reviews and Meta-Analysis (PRISMA) guidelines. We searched PubMed, Embase, Cochrane databases, and the American Society of Clinical Oncology (ASCO), European Society of Medical Oncology (ESMO), Society of Gynecologic Oncology (SGO) meeting abstracts, for randomized clinical trials using maintenance with PARP inhibitors in patients with advanced ovarian cancer, up to June 30, 2021. The measured outcomes were progression-free survival and safety (number and grade of adverse events), stratified by age (cut-off point: 65 years). Results A total of eight phase III trials were selected. Among the 4364 patients, 1435 (32.9%) were aged >= 65 (919 receiving PARP inhibitors, 516 receiving placebo). Compared with placebo, maintenance with PARP inhibitors improved progression-free survival in older patients (HR=0.54; 95% CI 0.45 to 0.65; p<0.00001). No differences were found in progression-free survival in comparison with a younger population (HR=0.47; p=0.13). Only hematologic adverse events were available for the age subgroups, and no differences emerged for all-grade hematologic adverse events (risk ratio (RR)=1.22, p=0.33 for anemia; RR=0.97, p=0.74 for neutropenia) and severe neutropenia (RR=0.97, p=0.86); old women were at lower risk of severe anemia (RR=0.79, p=0.04) but had a higher risk of severe thrombocytopenia (RR=1.27, p=0.01). Conclusions Maintenance with PARP inhibitors prolongs progression-free survival compared with placebo, both as monotherapy and combined with chemotherapy or bevacizumab, in older patients with advanced ovarian cancer (high-quality evidence). Hematologic safety is similar to that seen in younger patients. No overall survival data are available at this time. PROSPERO registration number CRD42021261039.