Efficacy of chemotherapy after progression during or following PARPi exposure in ovarian cancer☆

IF 7.1 2区医学 Q1 ONCOLOGY ESMO Open Pub Date : 2024-09-01 DOI:10.1016/j.esmoop.2024.103694

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Abstract

Background

Poly(ADP-ribose) polymerase inhibitors (PARPis) improved advanced ovarian cancer treatment. Most patients progress during or following PARPi exposure, however, with concerns about sensitivity of subsequent chemotherapy.

Patients and methods

In this international cohort study, we evaluated the efficacy of a subsequent chemotherapy following PARPi exposure in high-grade ovarian carcinoma patients. Endpoints included progression-free survival (PFS), overall survival and a multivariable Cox model was built to identify factors influencing PFS.

Results

We included 291 patients from four international centers treated between January 2002 and December 2021. The median number of previous chemotherapy was 1 (1.0-7.0), the median duration of PARPi exposure was 6.5 months (0.2-54.3 months). PARPi was used in first line in 14.1% patients. Most progressions occurred under PARPi exposure (89.1%). A BRCA pathogenic variant was identified in 130 patients (44.7%), absent in 157 patients (54.0%), and undocumented in 4 patients (1.4%). Platinum-based CT (PBC) and non-PBC were administered as subsequent treatments in, respectively, 182 patients (62.5%) and 109 patients (37.5%). Multivariable analyses showed that platinum-free interval (PFI) >6 months [adjusted hazards ratio (HR), 0.52; 95% confidence interval (CI) 0.39-0.70] and type of initial surgery (adjusted HR, 1.41; 95% CI 1.07-1.87; interval or closing surgery versus primary surgery) were associated with PFS, independent of BRCA status or line of therapy (≥2 versus 1). In patients with a PFI >6 months, PBC was numerically associated with the best PFS (adjusted HR, 0.68; 95% CI 0.46-1.01).

Conclusion

This is the largest real-world study assessing the efficacy of subsequent chemotherapy in patients progressing during PARPi exposure. The patients have poor outcomes. PBC is the best option in patients progressing on PARPi and eligible for PBC rechallenge (PFI >6 months).

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卵巢癌患者在接受 PARPi 治疗期间或之后病情恶化，化疗的疗效如何☆？

背景聚（ADP-核糖）聚合酶抑制剂（PARPis）改善了晚期卵巢癌的治疗。患者和方法在这项国际队列研究中，我们评估了高级别卵巢癌患者接受 PARPi 治疗后接受后续化疗的疗效。终点包括无进展生存期（PFS）和总生存期，并建立了一个多变量 Cox 模型来确定影响 PFS 的因素。既往化疗次数中位数为1次（1.0-7.0次），PARPi接触时间中位数为6.5个月（0.2-54.3个月）。14.1%的患者在一线使用PARPi。大多数进展发生在PARPi应用期间（89.1%）。130例患者（44.7%）发现了BRCA致病变体，157例患者（54.0%）未发现该变体，4例患者（1.4%）未发现该变体。分别有 182 名患者（62.5%）和 109 名患者（37.5%）接受了铂类 CT（PBC）和非 PBC 作为后续治疗。多变量分析显示，无铂间期（PFI）6个月[调整后危险比（HR），0.52；95%置信区间（CI）0.39-0.70]和初始手术类型（调整后HR，1.41；95% CI 1.07-1.87；间期或关闭手术与初始手术）与PFS相关，与BRCA状态或治疗方案（≥2与1）无关。在PFI >6个月的患者中，PBC在数字上与最佳PFS相关（调整后HR，0.68；95% CI 0.46-1.01）。患者的预后较差。对于PARPi治疗进展且符合PBC再挑战（PFI >6个月）条件的患者，PBC是最佳选择。

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.