Therapeutic Research

Abstract

Background and Objective：Olaparib is an oral molecular‒targeted drug that selectively inhibits poly（adenosine diphosphate‒ribose）polymerase（PARP）, the chief enzyme involved in DNA single‒strand break repair. An all‒patient use‒results surveillance of olaparib was conducted to investigate its safety and efficacy in actual clinical use. 　　Method：Patients who started olaparib during the registration period were registered in this all‒cases surveillance using a central registration method. With an observation period of 1 year, patient demographics, olaparib dosing status, adverse drug reactions（ADRs）, and best overall response, among other outcomes, were recorded. 　　Results：Patients with case report forms locked between April 18, 2018 and December 15, 2020 were analyzed. Among 838 patients［age 63.0 years, observation period 8.44 months, duration of exposure 7.47 months（all medians）］included in the safety population, ADRs occurred in 663 patients（79.1％）, with the most common being anemia in 332 patients（39.6％）, nausea in 286 patients（34.1％）, and fatigue in 105 patients （12.5％）. The most common serious ADRs were anemia in 107 patients（12.8％）, nausea in 16 patients（1.9％）, and platelet count decreased in 10 patients（1.2％）. ADRs leading to discontinuation were anemia in 31 patients, nausea in 27 patients, fatigue in 17 patients, and vomiting in 12 patients. Interstitial lung disease, secondary malignancies and myelosuppression, which were listed in the safety specifications for olaparib, occurred in 12 patients（1.4％）, 10 patients（1.2％）and 415 patients（49.5％）, respectively. Among 133 patients with renal impairment, ADRs occurred in 113 patients （85.0％）. The best overall response was evaluable in 628 patients in the efficacy population at the end of the 1‒year observation period, at which time the objective response rate was 36.0％（226 patients）and the disease control rate was 61.1％（384 patients）. In the efficacy population（808 patients）, the rate of disease progression at the end of the 1‒year observation period was 51.7％（418 patients）. The data collected were limited due to the design of the clinical experience investigation；therefore, subgroup analyses of efficacy according to gene mutation or number of prior lines, for example, were not possible. 　　Conclusion：No new safety signals that would affect the benefit‒risk balance of olaparib were found in this all‒patient use‒results surveillance. The efficacy of olaparib was consistent with prior clinical studies in patients with platinum‒sensitive recurrent ovarian cancer.