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
{"title":"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。","authors":"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","doi":"10.1016/j.euo.2024.09.013","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Key findings and limitations</h3><div>The median rPFS in asymptomatic/mildly symptomatic patients (<em>n</em> = 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 (<em>n</em> = 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.</div></div><div><h3>Conclusions and clinical implications</h3><div>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.</div></div><div><h3>Patient summary</h3><div>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.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 2","pages":"Pages 394-406"},"PeriodicalIF":8.3000,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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\",\"authors\":\"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\",\"doi\":\"10.1016/j.euo.2024.09.013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background and objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Key findings and limitations</h3><div>The median rPFS in asymptomatic/mildly symptomatic patients (<em>n</em> = 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 (<em>n</em> = 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.</div></div><div><h3>Conclusions and clinical implications</h3><div>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.</div></div><div><h3>Patient summary</h3><div>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.</div></div>\",\"PeriodicalId\":12256,\"journal\":{\"name\":\"European urology oncology\",\"volume\":\"8 2\",\"pages\":\"Pages 394-406\"},\"PeriodicalIF\":8.3000,\"publicationDate\":\"2024-10-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European urology oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2588931124002220\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European urology oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2588931124002220","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
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.
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