PDF(Pubmed)
Abstract：
BACKGROUND: Maintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, has been shown to extend progression-free survival in patients with newly diagnosed advanced ovarian cancer who responded to first-line platinum-based chemotherapy, regardless of biomarker status. However, there are limited data on niraparib\'s efficacy and safety in the neoadjuvant setting. The objective of Cohort C of the OPAL trial (OPAL-C) is to evaluate the efficacy, safety, and tolerability of neoadjuvant niraparib treatment compared with neoadjuvant platinum-taxane doublet chemotherapy in patients with newly diagnosed stage III/IV ovarian cancer with confirmed homologous recombination-deficient tumors.
METHODS: OPAL is an ongoing global, multicenter, randomized, open-label, phase 2 trial. In OPAL-C, patients will be randomized 1:1 to receive three 21-day cycles of either neoadjuvant niraparib or platinum-taxane doublet neoadjuvant chemotherapy per standard of care. Patients with a complete or partial response per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) will then undergo interval debulking surgery; patients with stable disease may proceed to interval debulking surgery or alternative therapy at the investigator\'s discretion. Patients with disease progression will exit the study treatment and proceed to alternative therapy at the investigator\'s discretion. After interval debulking surgery, all patients will receive up to three 21-day cycles of platinum-taxane doublet chemotherapy followed by niraparib maintenance therapy for up to 36 months. Adult patients with newly diagnosed stage III/IV ovarian cancer eligible to receive neoadjuvant platinum-taxane doublet chemotherapy followed by interval debulking surgery may be enrolled. Patients must have tumors that are homologous recombination-deficient. The primary endpoint is the pre-interval debulking surgery unconfirmed overall response rate, defined as the investigator-assessed percentage of patients with unconfirmed complete or partial response on study treatment before interval debulking surgery per RECIST v1.1.
CONCLUSIONS: OPAL-C explores the use of niraparib in the neoadjuvant setting as an alternative to neoadjuvant platinum-taxane doublet chemotherapy to improve postsurgical residual disease outcomes for patients with ovarian cancer with homologous recombination-deficient tumors. Positive findings from this approach could significantly impact preoperative ovarian cancer therapy, particularly for patients who are ineligible for primary debulking surgery.
BACKGROUND: ClinicalTrials.gov NCT03574779. Registered on February 28, 2022.
METHODS: OPAL is an ongoing global, multicenter, randomized, open-label, phase 2 trial. In OPAL-C, patients will be randomized 1:1 to receive three 21-day cycles of either neoadjuvant niraparib or platinum-taxane doublet neoadjuvant chemotherapy per standard of care. Patients with a complete or partial response per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) will then undergo interval debulking surgery; patients with stable disease may proceed to interval debulking surgery or alternative therapy at the investigator\'s discretion. Patients with disease progression will exit the study treatment and proceed to alternative therapy at the investigator\'s discretion. After interval debulking surgery, all patients will receive up to three 21-day cycles of platinum-taxane doublet chemotherapy followed by niraparib maintenance therapy for up to 36 months. Adult patients with newly diagnosed stage III/IV ovarian cancer eligible to receive neoadjuvant platinum-taxane doublet chemotherapy followed by interval debulking surgery may be enrolled. Patients must have tumors that are homologous recombination-deficient. The primary endpoint is the pre-interval debulking surgery unconfirmed overall response rate, defined as the investigator-assessed percentage of patients with unconfirmed complete or partial response on study treatment before interval debulking surgery per RECIST v1.1.
CONCLUSIONS: OPAL-C explores the use of niraparib in the neoadjuvant setting as an alternative to neoadjuvant platinum-taxane doublet chemotherapy to improve postsurgical residual disease outcomes for patients with ovarian cancer with homologous recombination-deficient tumors. Positive findings from this approach could significantly impact preoperative ovarian cancer therapy, particularly for patients who are ineligible for primary debulking surgery.
BACKGROUND: ClinicalTrials.gov NCT03574779. Registered on February 28, 2022.
摘要：
背景：尼拉帕尼维持治疗，聚（ADP-核糖）聚合酶抑制剂，已被证明可以延长对一线铂类化疗有反应的新诊断晚期卵巢癌患者的无进展生存期，无论生物标志物的状态。然而,关于尼拉帕尼在新辅助治疗中的疗效和安全性的数据有限.OPAL试验（OPAL-C）队列C的目的是评估疗效，安全,与新辅助铂-紫杉烷双重化疗相比，新辅助尼拉帕尼治疗在新诊断的III/IV期卵巢癌患者中的耐受性证实同源重组缺陷肿瘤。
方法：OPAL是一个正在进行的全球性，多中心，随机化，开放标签，第二阶段试验。在OPAL-C中,根据标准治疗,患者将被1:1随机分组,接受3个21天周期的尼拉帕尼或铂-紫杉烷双联新辅助化疗.根据实体瘤1.1版（RECISTv1.1）中的反应评估标准，具有完全或部分反应的患者将接受间隔减积手术；病情稳定的患者可以根据研究者的判断进行间隔减积手术或替代疗法。疾病进展的患者将退出研究治疗，并根据研究者的判断进行替代疗法。间隔减积手术后，所有患者将接受3个为期21天的铂类-紫杉烷双重化疗周期,随后接受尼拉帕尼维持治疗长达36个月.新诊断的III/IV期卵巢癌的成年患者可以接受新辅助铂-紫杉烷双联化疗，然后进行间隔减积手术。患者必须具有同源重组缺陷的肿瘤。主要终点是间隔前减积手术未确认的总体反应率，定义为根据RECISTv1.1进行的间隔减积手术前，研究者评估的研究治疗中未经证实的完全或部分反应的患者百分比。
结论：OPAL-C探讨了尼拉帕尼在新辅助治疗中的应用，作为新辅助铂-紫杉烷双重化疗的替代方案，以改善具有同源重组缺陷肿瘤的卵巢癌患者的术后残留疾病预后。这种方法的阳性结果可以显着影响术前卵巢癌治疗，特别是对于不符合初次减积手术资格的患者。
背景：ClinicalTrials.govNCT03574779。2022年2月28日注册。
方法：OPAL是一个正在进行的全球性，多中心，随机化，开放标签，第二阶段试验。在OPAL-C中,根据标准治疗,患者将被1:1随机分组,接受3个21天周期的尼拉帕尼或铂-紫杉烷双联新辅助化疗.根据实体瘤1.1版（RECISTv1.1）中的反应评估标准，具有完全或部分反应的患者将接受间隔减积手术；病情稳定的患者可以根据研究者的判断进行间隔减积手术或替代疗法。疾病进展的患者将退出研究治疗，并根据研究者的判断进行替代疗法。间隔减积手术后，所有患者将接受3个为期21天的铂类-紫杉烷双重化疗周期,随后接受尼拉帕尼维持治疗长达36个月.新诊断的III/IV期卵巢癌的成年患者可以接受新辅助铂-紫杉烷双联化疗，然后进行间隔减积手术。患者必须具有同源重组缺陷的肿瘤。主要终点是间隔前减积手术未确认的总体反应率，定义为根据RECISTv1.1进行的间隔减积手术前，研究者评估的研究治疗中未经证实的完全或部分反应的患者百分比。
结论：OPAL-C探讨了尼拉帕尼在新辅助治疗中的应用，作为新辅助铂-紫杉烷双重化疗的替代方案，以改善具有同源重组缺陷肿瘤的卵巢癌患者的术后残留疾病预后。这种方法的阳性结果可以显着影响术前卵巢癌治疗，特别是对于不符合初次减积手术资格的患者。
背景：ClinicalTrials.govNCT03574779。2022年2月28日注册。
