Age-Related Differences in Severe Adverse Events During Maintenance Therapy with PARP Inhibitors: A Retrospective Cohort Study in Japanese Patients with Ovarian Cancer
Advanced ovarian cancer carries a poor prognosis despite standard surgery and chemotherapy. Although poly (ADP-ribose) polymerase (PARP) inhibitors, such as olaparib and niraparib, have recently become standard maintenance therapy, they can cause hematologic and non-hematologic toxicities, and data on their safety in older Japanese patients are limited. We aimed to evaluate the incidence of clinically significant severe adverse events (SAEs), treatment interruptions, and discontinuation of PARP inhibitor maintenance therapy according to age in Japanese patients with ovarian cancer. This retrospective cohort study used data from the Japanese Diagnosis Procedure Combination database. Patients diagnosed with ovarian cancer who received treatment with PARP inhibitors approved in Japan (olaparib, olaparib plus bevacizumab, or niraparib) after surgery and chemotherapy were included. Clinically significant SAEs were identified using diagnostic and billing codes rather than laboratory-confirmed Common Terminology Criteria for Adverse Events (CTCAE) grading. Outcomes were assessed across two age groups (< 65 vs. ≥ 65 years) using inverse probability weighting to account for baseline differences. After adjustment, the baseline characteristics were balanced among the 1083 patients included in this study (olaparib, 315; olaparib plus bevacizumab, 343; niraparib, 425). In the olaparib group, patients aged ≥ 65 years showed a higher incidence of clinically significant neutropenia compared with those aged < 65 years (incidence rate ratio 7.47; 95% confidence interval 2.37-23.5). In contrast, no significant age-related differences were observed in the incidence of other clinically significant SAEs. Rates of hospitalization, treatment interruption, and treatment discontinuation were generally comparable between the age groups across all regimens. Overall, PARP inhibitor maintenance therapy appeared to be generally tolerated in older patients in this real-world cohort. However, older individuals who received olaparib monotherapy experienced a significantly higher incidence of clinically significant neutropenia, indicating the need for careful monitoring and individualized dose management in this subgroup.
