Phase II pilot study of the prednisone to dexamethasone switch in metastatic castration-resistant prostate cancer (mCRPC) patients with limited progression on abiraterone plus prednisone (SWITCH study).
Phase II pilot study of the prednisone to dexamethasone switch in metastatic castration-resistant prostate cancer (mCRPC) patients with limited progression on abiraterone plus prednisone (SWITCH study).
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DOI：
10.1038/s41416-018-0123-9
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发表时间：
2018-10
影响因子：
8.8
通讯作者：
Olmos D
中科院分区：
文献类型：
--
作者：
Romero-Laorden N;Lozano R;Jayaram A;López-Campos F;Saez MI;Montesa A;Gutierrez-Pecharoman A;Villatoro R;Herrera B;Correa R;Rosero A;Pacheco MI;Garcés T;Cendón Y;Nombela MP;Van de Poll F;Grau G;Rivera L;López PP;Cruz JJ;Lorente D;Attard G;Castro E;Olmos D
尽管大多数转移性去势抵抗性前列腺癌（mCRPC）患者受益于醋酸阿比特龙加泼尼松5 mg bid（AA + P），但最终会发生耐药。长期使用泼尼松已被认为是驱动耐药性的机制之一，这可能会通过切换到另一种类固醇来逆转。研究是一项单组、开放标签、单阶段II期研究。主要目的是在进展为AA + P的mCRPC患者中评价醋酸阿比特龙+地塞米松0.5 mg每日一次（AA + D）的抗肿瘤活性。接受AA + P治疗至少12周后，具有前列腺特异性抗原（PSA）和/或放射学进展有限的临床稳定mCRPC患者有资格入选。主要终点测量为AA + D治疗6周后PSA较基线下降≥ 30%（PSA 30）的患者比例。次要终点包括：12周时的PSA 50应答率、至生化和放射学进展的时间、总生存期、安全性特征评价、后续治疗线的获益和应答生物标志物的鉴定（AR拷贝数、TMPRSS 2-ERG状态和PTEN表达）。26例患者入组。PSA 30和PSA 50分别为46.2%和34.6%。至生化和放射学进展的中位时间分别为5.3和11.8个月。观察到两种放射学反应。中位总生存期为20.9个月。在血浆循环肿瘤DNA中检测到AR增益的患者对转换没有反应，而AR正常状态的患者受益最多。未观察到明显的毒性，对后续紫杉烷的PSA 50应答率为50%。在选定的AA + P治疗期间疾病进展有限的临床稳定mCRPC患者中，类固醇从泼尼松转换为地塞米松可导致PSA和放射学缓解。
Despite most metastatic castration-resistant prostate cancer (mCRPC) patients benefit from abiraterone acetate plus prednisone 5 mg bid (AA + P), resistance eventually occurs. Long-term use of prednisone has been suggested as one of the mechanisms driving resistance, which may be reversed by switching to another steroid. SWITCH was a single-arm, open-label, single-stage phase II study. The primary objective was to evaluate the antitumour activity of abiraterone acetate plus dexamethasone 0.5 mg daily (AA + D) in mCRPC patients progressing to AA + P. Clinically stable mCRPC patients who had prostate-specific antigen (PSA) and/or limited radiographic progression after at least 12 weeks on AA + P, were eligible. The primary endpoint was measured as the proportion of patients achieving a PSA decline of ≥ 30% (PSA30) from baseline after 6 weeks on AA + D. Secondary endpoints included: PSA50 response rate at 12 weeks, time to biochemical and radiological progression, overall survival, safety profile evaluation, benefit from subsequent treatment lines and the identification of biomarkers of response (AR copy number, TMPRSS2-ERG status and PTEN expression). Twenty-six patients were enrolled. PSA30 and PSA50 were 46.2% and 34.6%, respectively. Median time to biochemical and radiological progression were 5.3 and 11.8 months, respectively. Two radiological responses were observed. Median overall survival was 20.9 months. Patients with AR gain detected in plasma circulating tumour DNA did not respond to switch, whereas patients with AR normal status benefited the most. No significant toxicities were observed and PSA50 response rate to subsequent taxane was 50%. In selected clinical stable mCRPC patients with limited disease progression on AA + P, a steroid switch from prednisone to dexamethasone can lead to PSA and radiological responses.
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DOI：
10.1093/annonc/mdv257
发表时间：
2015-08
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Gillessen S;Omlin A;Attard G;de Bono JS;Efstathiou E;Fizazi K;Halabi S;Nelson PS;Sartor O;Smith MR;Soule HR;Akaza H;Beer TM;Beltran H;Chinnaiyan AM;Daugaard G;Davis ID;De Santis M;Drake CG;Eeles RA;Fanti S;Gleave ME;Heidenreich A;Hussain M;James ND;Lecouvet FE;Logothetis CJ;Mastris K;Nilsson S;Oh WK;Olmos D;Padhani AR;Parker C;Rubin MA;Schalken JA;Scher HI;Sella A;Shore ND;Small EJ;Sternberg CN;Suzuki H;Sweeney CJ;Tannock IF;Tombal B
通讯作者：
Tombal B
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
8.8
作者：
Lorente, D.;Omlin, A.;Ferraldeschi, R.;Pezaro, C.;Perez, R.;Mateo, J.;Altavilla, A.;Zafeirou, Z.;Tunariu, N.;Parker, C.;Dearnaley, D.;Gillessen, S.;de Bono, J.;Attard, G.
通讯作者：
Attard, G.
影响因子：
45.3
作者：
Reid, Alison H. M.;Attard, Gerhardt;de Bono, Johann S.
通讯作者：
de Bono, Johann S.
影响因子：
6.4
作者：
Steketee, K;Timmerman, L;Trapman, J
通讯作者：
Trapman, J