奥拉帕利加阿比特龙与安慰剂加阿比特龙一线治疗无症状/轻度症状和症状转移性钙化抵抗性前列腺癌患者的疗效和安全性:PROpel 3 期试验分析。

IF 8.3 1区 医学 Q1 ONCOLOGY
Noel W. Clarke , Andrew J. Armstrong , Mototsugu Oya , Neal Shore , Giuseppe Procopio , João Daniel Guedes , Cagatay Arslan , Niven Mehra , Francis Parnis , Emma Brown , Friederike Schlürmann , Jae Young Joung , Mikio Sugimoto , Oliver Sartor , Christian Poehlein , David McGuinness , Arnold Degboe , Fred Saad
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引用次数: 0

摘要

背景和目的:在PROpel (NCT03732820)中,奥拉帕利+阿比特龙与安慰剂+阿比特龙相比,一线(1L)转移性去势抵抗性前列腺癌(mCRPC)患者的放射学无进展生存期(rPFS)获益具有统计学意义,总生存期(OS)也有所延长。在此,我们报告了对基线时无症状/轻度症状或有症状的患者进行的事后探索性亚组分析:患者按 1:1 随机分配至奥拉帕利(300 毫克,每天两次)或安慰剂与阿比特龙(1000 毫克,每天一次)+ 泼尼松/泼尼松龙(5 毫克,每天两次)。在这项事后探索性分析中,患者的简明疼痛量表-简表(BPI-SF)第3项得分达到了主要研究结果和局限性:在无症状/轻度症状患者(n = 560)中,奥拉帕利+阿比特龙的中位rPFS为27.6个月,安慰剂+阿比特龙为19.1个月(危险比[HR],0.59;95%置信区间[CI],0.46-0.76)。对于无症状患者(n = 183),等效值为14.1个月对13.8个月(HR,0.78;95% CI,0.54-1.13)。在最终计划的OS分析中,奥拉帕利+阿比特龙未达到无症状/轻度症状患者的中位OS,而安慰剂+阿比特龙为39.5个月(HR,0.77;95% CI,0.59-1.00)。对于无症状患者,等效值为22.9个月对22.8个月(HR,0.82;95% CI,0.58-1.16)。其他结果显示亚组间无明显差异:奥拉帕利+阿比特龙为无症状/轻度症状或有症状的1L mCRPC患者带来了疗效益处。患者摘要:PROpel是一项3期临床试验,与安慰剂加阿比特龙相比,该试验研究了奥拉帕利与阿比特龙联合用药是否能延缓患者的癌症进展。有或没有转移性耐受性前列腺癌疼痛症状的患者均可参加该试验。结果显示,奥拉帕利加阿比特龙可降低疾病进展和死亡风险,与有疼痛症状的患者相比,无疼痛症状或有轻微疼痛症状的患者获益更大。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Efficacy and Safety of Olaparib Plus Abiraterone Versus Placebo Plus Abiraterone in the First-line Treatment of Patients with Asymptomatic/Mildly Symptomatic and Symptomatic Metastatic Castration-resistant Prostate Cancer: Analyses from the Phase 3 PROpel Trial

Background and objective

In PROpel (NCT03732820), olaparib + abiraterone resulted in a statistically significant radiographic progression-free survival (rPFS) benefit and numerically prolonged overall survival (OS) versus placebo + abiraterone in first-line (1L) metastatic castration-resistant prostate cancer (mCRPC) patients. Here, we report post hoc exploratory subgroup analyses in patients with asymptomatic/mildly symptomatic or symptomatic disease at baseline.

Methods

Patients were randomised 1:1 to olaparib (300 mg b.i.d.) or placebo with abiraterone (1000 mg o.d.) + prednisone/prednisolone (5 mg b.i.d.). For this post hoc exploratory analysis, patients with a Brief Pain Inventory—Short Form (BPI-SF) item 3 score of <4 and no opiate use were classified as asymptomatic/mildly symptomatic; those with a BPI-SF item 3 score of ≥4 and/or opiate use were classified as symptomatic. Subgroup analyses included investigator-assessed rPFS, OS, objective response rate, time to second progression or death, health-related quality of life, and safety.

Key findings and limitations

The median rPFS in asymptomatic/mildly symptomatic patients (n = 560) was 27.6 mo for olaparib + abiraterone versus 19.1 mo for placebo + abiraterone (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.46–0.76). For symptomatic patients (n = 183), equivalent values were 14.1 versus 13.8 mo (HR, 0.78; 95% CI, 0.54–1.13). At the final planned OS analysis, the median OS in asymptomatic/mildly symptomatic patients was not reached for olaparib + abiraterone versus 39.5 mo for placebo + abiraterone (HR, 0.77; 95% CI, 0.59–1.00). For symptomatic patients, equivalent values were 22.9 versus 22.8 mo (HR, 0.82; 95% CI, 0.58–1.16). Other outcomes showed no meaningful differences between the subgroups.

Conclusions and clinical implications

Olaparib + abiraterone provided efficacy benefits in 1L mCRPC patients with either asymptomatic/mildly symptomatic or symptomatic disease. A larger benefit occurred in asymptomatic/mildly symptomatic patients.

Patient summary

PROpel, a phase 3 clinical trial, looked at whether combining olaparib with abiraterone delays the progression of patients’ cancer compared with placebo plus abiraterone. Patients with or without pain symptoms associated with metastatic castration-resistant prostate cancer were eligible for enrolment into the trial. Results showed that olaparib plus abiraterone reduced the risk of disease progression and death, with a larger benefit observed in patients without or with mild pain symptoms than in those with pain symptoms.
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来源期刊
CiteScore
15.50
自引率
2.40%
发文量
128
审稿时长
20 days
期刊介绍: Journal Name: European Urology Oncology Affiliation: Official Journal of the European Association of Urology Focus: First official publication of the EAU fully devoted to the study of genitourinary malignancies Aims to deliver high-quality research Content: Includes original articles, opinion piece editorials, and invited reviews Covers clinical, basic, and translational research Publication Frequency: Six times a year in electronic format
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