Cabazitaxel versus abiraterone or enzalutamide in poor prognosis metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase II trial

被引：51

作者：

Annala, M. ^{[1
,2
,3
]}

Fu, S. ^{[4
,5
]}

Bacon, J. V. W. ^{[1
]}

Sipola, J. ^{[2
,3
]}

Iqbal, N. ^{[6
]}

Ferrario, C. ^{[7
]}

Ong, M. ^{[8
,9
]}

Wadhwa, D. ^{[10
]}

Hotte, S. J. ^{[11
]}

Lo, G. ^{[12
]}

Tran, B. ^{[13
]}

Wood, L. A. ^{[14
]}

Gingerich, J. R. ^{[15
]}

North, S. A. ^{[16
]}

Pezaro, C. J. ^{[17
,18
]}

Ruether, J. D. ^{[19
]}

Sridhar, S. S. ^{[20
]}

Kallio, H. M. L. ^{[2
,3
]}

Khalaf, D. J. ^{[4
]}

Wong, A. ^{[1
]}

Beja, K. ^{[1
]}

Schonlau, E. ^{[1
]}

Taavitsainen, S. ^{[2
,3
]}

Nykter, M. ^{[2
,3
]}

Vandekerkhove, G. ^{[1
]}

Azad, A. A. ^{[13
]}

Wyatt, A. W. ^{[1
,21
]}

Chi, K. N. ^{[1
,4
]}

机构：

[1] Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, 2660 Oak St, Vancouver, BC V6H 3Z6, Canada

[2] Tampere Univ, Fac Med & Hlth Technol, Tampere, Finland

[3] Tays Canc Ctr, Tampere, Finland

[4] BC Canc, Dept Med Oncol, 600 West 10th Ave,Vancouver, Vancouver, BC V5Z 4E6, Canada

[5] Univ Auckland, Sch Med Sci, Oncol, Auckland, New Zealand

[6] Univ Saskatchewan, Saskatoon Canc Ctr, Med Oncol, Saskatoon, SK, Canada

[7] McGill Univ, Jewish Gen Hosp, Montreal, PQ, Canada

[8] Ottawa Hosp, Dept Med, Div Med Oncol, Ottawa, ON, Canada

[9] Univ Ottawa, Ottawa, ON, Canada

[10] BC Canc Kelowna Ctr, Kelowna, BC, Canada

[11] Juravinski Canc Ctr, Oncol, Hamilton, ON, Canada

[12] Lakeridge Hlth, Dept Med Oncol, RS McLaughlin Durham Reg Canc Ctr, Oshawa, ON, Canada

[13] Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia

[14] QEII Hlth Sci Ctr, Halifax, NS, Canada

[15] Canc Care Manitoba, Dept Med Oncol & Hematol, Winnipeg, MB, Canada

[16] Univ Alberta, Dept Oncol, Edmonton, AB, Canada

[17] Monash Univ, Eastern Hlth Clin Sch, Melbourne, Vic, Australia

[18] Eastern Hlth, Dept Oncol, Melbourne, Vic, Australia

[19] Tom Baker Canc Clin, Calgary, AB, Canada

[20] Princess Margaret Canc Ctr, Dept Med Oncol & Hematol, Toronto, ON, Canada

[21] BC Canc, Michael Smith Genome Sci Ctr, Vancouver, BC, Canada

来源：

ANNALS OF ONCOLOGY | 2021年 / 32卷 / 07期

基金：

芬兰科学院; 加拿大健康研究院;

关键词：

taxane chemotherapy; androgen receptor pathway inhibitor; plasma cell-free DNA; circulating tumor DNA (ctDNA); prostate cancer; SURVIVAL; OUTCOMES; MODEL; MEN; ACETATE; DNA;

D O I：

10.1016/j.annonc.2021.03.205

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Treatment of poor prognosis metastatic castration-resistant prostate cancer (mCRPC) includes taxane chemotherapy and androgen receptor pathway inhibitors (ARPI). We sought to determine optimal treatment in this setting. Patients and methods: This multicentre, randomised, open-label, phase II trial recruited patients with ARPI-naive mCRPC and poor prognosis features (presence of liver metastases, progression to mCRPC after <12 months of androgen deprivation therapy, or >= 4 of 6 clinical criteria). Patients were randomly assigned 1 : 1 to receive cabazitaxel plus prednisone (group A) or physician's choice of enzalutamide or abiraterone plus prednisone (group B) at standard doses. Patients could cross over at progression. The primary endpoint was clinical benefit rate for first-line treatment (defined as prostate-specific antigen response >= 50%, radiographic response, or stable disease >= 12 weeks). Results: Ninety-five patients were accrued (median follow-up 21.9 months). First-line clinical benefit rate was greater in group A versus group B (80% versus 62%, P = 0.039). Overall survival was not different between groups A and B (median 37.0 versus 15.5 months, hazard ratio (HR) 0.58, P = 0.073) nor was time to progression (median 5.3 versus 2.8 months, HR 0.87, P = 0.52). The most common first-line treatment-related grade >3 adverse events were neutropenia (cabazitaxel 32% versus ARPI 0%), diarrhoea (9% versus 0%), infection (9% versus 0%), and fatigue (7% versus 5%). Baseline circulating tumour DNA (ctDNA) fraction above the cohort median and on-treatment ctDNA increase were associated with shorter time to progression (HR = 2.38, P < 0.001; HR = 4.03, P < 0.001). Patients with >30% ctDNA fraction at baseline had markedly shorter overall survival than those with undetectable ctDNA (HR = 38.22, P < 0.001). Conclusions: Cabazitaxel was associated with a higher clinical benefit rate in patients with ARPI-naive poor prognosis mCRPC. ctDNA abundance was prognostic independent of clinical features, and holds promise as a stratification biomarker.

引用

页码：896 / 905

页数：10

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