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

Abstract

BackgroundPoly-(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.ObjectiveTo assess the efficacy and safety of PARP inhibitors versus placebo as maintenance therapy in older patients with ovarian cancer.MethodsThis 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).ResultsA 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).ConclusionsMaintenance 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 numberCRD42021261039.

Dose reduction of olaparib in older patients: Insights from an analysis of a National Database in Japan

“…While a previous systematic review of olaparib use on ovarian cancer patients reported that approximately one-third of patients (1435/4364) in eight RCTs were 65 years or older, and hematologic safety was similar to that seen in younger patients. 6 Another subgroup analysis of an RCT found that older patients enrolled in PAOLA-1 achieved similar progression-free survival benefits compared with younger patients, with a similar safety profile. 7 There are several potential reasons for this practice.…”

“…A systematic review of olaparib use on ovarian cancer patients reported that approximately one-third of patients (1435/4364) in eight RCTs were 65 years or older, and hematologic safety was similar to that seen in younger patients. 6 Another subgroup analysis of an RCT found that older patients enrolled in PAOLA-1 achieved similar progression-free survival benefits compared with younger patients, with a similar safety profile. 7 Thus, though studies have evaluated the effects of olaparib on the elderly population, these evaluations are limited to subgroup analyses in the setting of an RCT, and there is a dearth of real-world evidence on the use of olaparib in aging populations, especially those using national-level data.…”

Equitable inclusion of diverse populations in oncology clinical trials: deterrents and drivers

“…Recent research showed that older patients benefit from poly (ADP-ribose) polymerase inhibitor therapy, leading to prolonged progression-free survival similar to younger patients with comparable hematologic safety profiles. 30 …”

PARP inhibitors: risk factors for toxicity and matching patients to the proper poly (ADP-ribose) polymerase inhibitor (PARPi) therapy

“…Interestingly, a meta-analysis which included results from clinical trials investigating PARPi given as monotherapy or combined with chemotherapy and/or anti-angiogenic drugs compared PARPi with placebo in an elderly cohort aged ≥65 years and in younger patients aged <65 years 57. In this study, safety information was limited to hematologic toxicity and a lower risk of severe anemia was reported in older patients (p=0.04) 57. However, real-world studies should include more geriatric assessment.…”