Niraparib在日本接受大量治疗、同源重组缺失的卵巢癌患者中的应用：多中心第2期研究的最终结果

Niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer: final results of a multicenter phase 2 study

Journal of Gynecologic Oncology

影响因子:3.7

分区:医学2区 / 妇产科学3区肿瘤学3区

发表日期:2024 Sep

作者: Daisuke Aoki, Tsutomu Tabata, Satoshi Yanagida, Toshiaki Nakamura, Eiji Kondo, Junzo Hamanishi, Kenichi Harano, Kosei Hasegawa, Takeshi Hirasawa, Kensuke Hori, Shinichi Komiyama, Motoki Matsuura, Hidekatsu Nakai, Hiroko Nakamura, Jun Sakata, Kazuhiro Takehara, Munetaka Takekuma, Yoshihito Yokoyama, Yoichi Kase, Shuuji Sumino, Junpei Soeda, Ai Kato, Ajit Suri, Aikou Okamoto, Toru Sugiyama

DOI: 10.3802/jgo.2024.35.e114

摘要

评价尼拉帕利在日本大量治疗、同源重组缺失的卵巢癌患者中的长期疗效和安全性。本研究为一项第2期、多中心、开放标签、单臂研究的后续分析，纳入符合条件的日本女性患者，具有同源重组缺失、铂敏感、复发的高级浆液型上皮卵巢癌、输卵管癌或原发性腹膜癌，患者完成了3-4线化疗且未接受过多肽ADP核糖聚合酶抑制剂治疗。患者每日一次口服尼拉帕利（起始剂量300 mg），持续28天的周期，直至确诊疾病进展、出现不可接受的毒性或患者撤回同意。主要终点为经确认的客观反应率（ORR），按《实体瘤反应评价标准第1.1版》评估。安全性评价包括治疗引发的副作用（TEAEs）。共入组20名患者，纳入疗效和安全性分析。中位研究持续时间为759.5天。中位剂量强度为201.3 mg/天。经确认的ORR为60.0%（90%置信区间[CI]=39.4-78.3）；2例完全缓解，10例部分缓解。缓解的中位持续时间为9.9个月（95% CI=3.9-26.9），疾病控制率为90.0%（95% CI=68.3-98.8）。最常见的TEAEs为贫血（n=15）、恶心（n=12）和血小板减少（n=11）。因副作用导致的治疗剂量减少、暂停或停药的患者分别为16（80.0%）、15（75.0%）和2（10.0%）。尼拉帕利的长期疗效和安全性与非日本患者相似，未发现新的安全信号。ClinicalTrials.gov编号：NCT03759600。

Abstract

To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer.This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3-4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs).20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4-78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9-26.9) and the disease control rate was 90.0% (95% CI=68.3-98.8). The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively.The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.ClinicalTrials.gov Identifier: NCT03759600.