Analysis of clinical factors in olaparib-related anemia using adverse drug event reporting databases

Abstract

Abstract Purpose: Anemia is one of the dose-limiting toxicities of olaparib. The global phase Ⅲ trial confirmed that anemia occurrence in Japanese was relatively high. The factors related to anemia in different nationalities remain unknown. Therefore, this study investigated the factors of olaparib-related anemia in real-world settings using an adverse event reporting system database. Methods: We used data from FDA Adverse Events Reporting System (FAERS) and Japanese Adverse Drug Event Report database (JADER) between 2018 and 2021. FAERS reports from Japan were collected to conduct subgroup analyses, which was defined as FAERS-Japan. The endpoint was the occurrence of olaparib-related anemia. Disproportionality analysis was conducted to calculate reporting odds ratio (ROR), with a confidence interval of 95%. Adjusted ROR (aROR) was calculated to control for gender differences. Results: In FAERS and JADER, the daily olaparib dose per body weight (DPBW) ≥12 mg/kg was detected to be a positive signal for anemia occurrence (aROR; FAERS, 4.483 [3.009–6.680], p<0.001, FAERS-Japan, 1.834 [1.091–3.063], p=0.009, and JADER, 1.628 [1.039–2.551], p=0.034). Furthermore, FAERS reports confirmed that females with body weight <50kg, reports from Japan, concomitant use of drugs suppressing vitamin B12, and previous platinum treatment history were positive signals of olaparib-related anemia. FAERS-Japan also showed that body weight <50kg and previous platinum treatment history were positive signals for the anemia occurrence. Conclusion: High DPBW poses a significant risk of anemia. The co-administration of drugs suppressing vitamin B12 and previous platinum treatment history are also important information to evaluate the risk of olaparib-related anemia.