McKay Rana R, Zurita Amado J, Werner Lillian, Bruce Justine Y, Carducci Michael A, Stein Mark N, Heath Elisabeth I, Hussain Arif, Tran Hai T, Sweeney Christopher J, Ross Robert W, Kantoff Philip W, Slovin Susan F, Taplin Mary-Ellen
Rana R. McKay, Lillian Werner, Christopher J. Sweeney, Philip W. Kantoff, and Mary-Ellen Taplin, Dana-Farber Cancer Institute, Boston; Robert W. Ross, Bluebird Bio, Cambridge, MA; Amado J. Zurita and Hai T. Tran, MD Anderson Cancer Center, Houston, TX; Justine Y. Bruce, University of Wisconsin Carbone Cancer Center, Madison, WI; Michael A. Carducci, Johns Hopkins University; Arif Hussain, Greenebaum Cancer Center, Baltimore, MD; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Elisabeth I. Heath, Karmanos Cancer Institute, Detroit, MI; and Philip W. Kantoff and Susan F. Slovin, Memorial Sloan Kettering Cancer Center, New York, NY.
J Clin Oncol. 2016 Jun 1;34(16):1913-20. doi: 10.1200/JCO.2015.65.3154. Epub 2016 Apr 4.
Patients with recurrent prostate cancer after local treatment make up a heterogeneous population for whom androgen deprivation therapy (ADT) is the usual treatment. The purpose of this randomized phase II trial was to investigate the efficacy and toxicity of short-course ADT with or without bevacizumab in men with hormone-sensitive prostate cancer.
Eligible patients had an increasing prostate-specific antigen (PSA) of ≤ 50 ng/mL and PSA doubling time of less than 18 months. Patients had either no metastases or low burden, asymptomatic metastases (lymph nodes < 3 cm and five or fewer bone metastases). Patients were randomly assigned 2:1 to a luteinizing hormone-releasing hormone agonist, bicalutamide and bevacizumab or ADT alone, for 6 months. The primary end point was PSA relapse-free survival (RFS). Relapse was defined as a PSA of more than 0.2 ng/mL for prostatectomy patients or PSA of more than 2.0 ng/mL for primary radiation therapy patients.
Sixty-six patients received ADT + bevacizumab and 36 received ADT alone. Patients receiving ADT + bevacizumab had a statistically significant improvement in RFS compared with patients treated with ADT alone (13.3 months for ADT + bevacizumab v 10.2 months for ADT alone; hazard ratio, 0.47; 95% CI, 0.29 to 0.77; log-rank P = .002). Hypertension was the most common adverse event in patients receiving ADT + bevacizumab (36%).
ADT combined with bevacizumab resulted in an improved RFS for patients with hormone-sensitive prostate cancer. Long-term follow-up is needed to determine whether some patients have a durable PSA response and are able to remain off ADT for prolonged periods. Our data provide rationale for combining vascular endothelial growth factor-targeting therapy with ADT in hormone-sensitive prostate cancer.
局部治疗后复发的前列腺癌患者构成了一个异质性群体，雄激素剥夺疗法（ADT）是其常用治疗方法。这项随机II期试验的目的是研究在激素敏感性前列腺癌男性患者中，短期ADT联合或不联合贝伐单抗的疗效和毒性。
符合条件的患者前列腺特异性抗原（PSA）升高至≤50 ng/mL，且PSA倍增时间小于18个月。患者无转移或转移负担低、无症状转移（淋巴结<3 cm且骨转移灶为5个或更少）。患者按2:1随机分配接受促黄体生成素释放激素激动剂、比卡鲁胺和贝伐单抗，或仅接受ADT，为期6个月。主要终点是PSA无复发生存期（RFS）。复发定义为前列腺切除术后患者PSA超过0.2 ng/mL，或原发放射治疗患者PSA超过2.0 ng/mL。
66例患者接受ADT+贝伐单抗，36例患者仅接受ADT。与仅接受ADT治疗的患者相比，接受ADT+贝伐单抗的患者RFS有统计学显著改善（ADT+贝伐单抗组为13.3个月，ADT组为10.2个月；风险比，0.47；95%CI，0.29至0.77；对数秩检验P = 0.002）。高血压是接受ADT+贝伐单抗患者中最常见的不良事件（36%）。
ADT联合贝伐单抗可改善激素敏感性前列腺癌患者的RFS。需要进行长期随访以确定部分患者是否有持久的PSA反应，并能够长期停用ADT。我们的数据为在激素敏感性前列腺癌中将血管内皮生长因子靶向治疗与ADT联合应用提供了理论依据。
