Severe anemia as a risk factor in Japanese patients with ovarian cancer receiving olaparib: A retrospective study

Background: Ovarian cancer is often diagnosed at an advanced stage, and recurrence after initial platinum-based chemotherapy remains a major challenge. Olaparib, a poly (ADP-ribose) polymerase inhibitor, is an essential maintenance therapy, particularly for patients with homologous recombination deficiency, with proven efficacy. However, hematologic toxicity—especially anemia—is common and frequently leads to dose reductions or treatment interruptions. Japanese patients may be more susceptible to this toxicity because of smaller body size and potentially higher systemic drug exposure. Although dose reduction is recommended for patients with moderate renal impairment in Western guidelines, standardized criteria have not been established in Japan, and real-world evidence on predictors of severe anemia is limited. This study aimed to identify clinical factors associated with grade ≥ 3 anemia during olaparib therapy. Methods: We conducted a single-center retrospective cohort study of patients with ovarian cancer who initiated olaparib at Kobe City Medical Center General Hospital between July 2018 and December 2022. Patients who began therapy at external institutions were excluded. Adverse events were assessed using Common Terminology Criteria for Adverse Events version 5.0. Cox proportional hazards models were applied to evaluate predictors of grade ≥ 3 anemia, with statistical significance set at P  < 0.05. Results: Among the 75 patients included the median baseline creatinine clearance (Ccr) was 75.7 mL/min. Twenty-five patients (33%) had prior exposure to pegylated liposomal doxorubicin (PLD), and eight (11%) had a baseline Ccr < 50 mL/min. Grade ≥ 3 anemia developed in 33 patients (44%). Multivariate analysis identified prior PLD exposure (hazard ratio [HR] 4.37, 95% confidence interval [CI] 2.30–8.29), baseline Ccr < 50 mL/min (HR 4.03, 95% CI 1.53–10.63), and baseline Grade 2 anemia as independent predictors. Treatment duration was significantly shorter in patients with prior PLD exposure. Conclusion: Prior PLD therapy, impaired renal function, and pre-existing anemia substantially increased the risk of severe anemia during olaparib treatment. These findings highlight the need for risk-adaptive monitoring strategies and proactive management in patients with high risk for severe anemia. Further studies with larger cohorts of patients with renal impairment are recommended to support dose-adjustment strategies and optimize treatment safety.