Open-label phase II study evaluating the efficacy and safety of two doses of pertuzumab in castrate chemotherapy-naive patients with hormone-refractory prostate cancer
Open-label phase II study evaluating the efficacy and safety of two doses of pertuzumab in castrate chemotherapy-naive patients with hormone-refractory prostate cancer
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DOI：
10.1200/jco.2006.07.0888
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发表时间：
2007-01-20
影响因子：
45.3
通讯作者：
Graham, John
中科院分区：
文献类型：
--
作者：
de Bono, Johann Sebastian;Bellmunt, Joaquim;Graham, John
目的 确定激素难治性前列腺癌 (HRPC) 去势患者开始接受单药帕妥珠单抗治疗后 24 周内前列腺特异性抗原 (PSA) 50% 下降率。 患者和方法 采用两个独立的 Simon 两阶段设计来评估每 3 周静脉注射一次的两剂帕妥珠单抗。对第一组接受 420 mg（负荷剂量 840 mg）治疗的前 23 名可评估患者进行的中期分析表明，如果所有患者在完成至少三个周期的治疗后 PSA 下降 50%，或者在完成三个周期之前因治疗反应不足、死亡或研究相关毒性而退出，则允许终止额外入组。第二组接受 1,050 mg 治疗的患者可以采用相同的设计进行入组，如果超过 3 名患者的 PSA 下降≥ 50%，则将另外 27 名患者接受 1,050 mg 治疗。 结果 68 名已去势、未接受过化疗的 HRPC 男性入组。共有 35 名患者接受了 420 mg 的治疗；中期分析时未观察到 PSA 下降 >= 50%，招募已停止。随后共有 33 名患者接受了 1,050 mg 的治疗，中期分析中未观察到 PSA 下降 >= 50%。帕妥珠单抗的耐受性良好。结论 帕妥珠单抗在任一测试剂量水平下，对患有 HRPC 的去势患者没有临床显着的单药活性。这可能反映了驱动雄激素受体信号传导的前列腺内雄激素的显着水平的持续存在。
Purpose To determine the prostate-specific antigen (PSA) 50% decline rate within 24 weeks of starting treatment with single-agent pertuzumab in castrate patients with hormone-refractory prostate cancer (HRPC).Patients and Methods Two independent Simon's two-stage designs were used to evaluate two doses of pertuzumab administered intravenously once every 3 weeks. An interim analysis of the first 23 assessable patients in the first cohort treated at 420 mg (loading dose of 840 mg) allowed termination of additional enrollment if = 50% decline in PSA after all patients had completed at least three cycles of therapy or withdrew due to insufficient therapeutic response, death, or study-related toxicity before completing three cycles. A second cohort of patients treated at 1,050 mg could be enrolled with the same design, and if more than three patients had a >= 50% decline in PSA, 27 more patients would be treated at 1,050 mg.Results Sixty-eight castrate, chemotherapy-naive men with HRPC were enrolled. A total of 35 patients were treated at 420 mg; no PSA declines >= 50% were observed at the interim analysis and recruitment was stopped. A total of 33 patients were then treated at 1,050 mg, and no PSA declines >= 50% were observed at the interim analysis. Pertuzumab was well tolerated.Conclusion Pertuzumab has no clinically significant single-agent activity in castrate patients with HRPC at either of the tested dose levels. This may reflect the continued presence of significant levels of intraprostatic androgen driving androgen receptor signaling.