Phase II, Randomized Trial to Compare Anastrozole Combined with Gefitinib or Placebo in Postmenopausal Women with Hormone Receptor-Positive Metastatic Breast Cancer
Phase II, Randomized Trial to Compare Anastrozole Combined with Gefitinib or Placebo in Postmenopausal Women with Hormone Receptor-Positive Metastatic Breast Cancer
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DOI：
10.1158/1078-0432.ccr-09-2282
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发表时间：
2010-03-15
影响因子：
11.5
通讯作者：
Magill, Patrick J.
中科院分区：
文献类型：
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作者：
Cristofanilli, Massimo;Valero, Vicente;Magill, Patrick J.
目的：本II期随机试验评价了阿那曲唑联合吉非替尼或阿那曲唑与安慰剂治疗激素受体阳性转移性乳腺癌（MBC）的疗效和耐受性。实验设计：绝经后激素受体阳性可测量或可评估MBC的妇女，如果未接受过该疾病阶段的内分泌治疗，或在辅助他莫昔芬治疗期间/之后发生转移性疾病，则符合条件。主要反应变量是无进展生存期（PFS），次要反应变量包括临床获益率、客观反应率、总生存期、安全性和耐受性以及药代动力学。肿瘤生物标志物评价是一个探索性的objectives.Results：43例患者被随机分配到阿那曲唑加吉非替尼和50例患者被随机分配到阿那曲唑加安慰剂的计划共174例（招募提前停止，由于招募缓慢）。接受阿那曲唑和吉非替尼联合治疗的患者的PFS长于接受阿那曲唑+安慰剂治疗的患者[风险比（吉非替尼/安慰剂），0.55; 95%置信区间，0.32-0.94;中位PFS，14.7 vs 8.4个月]。阿那曲唑加吉非替尼和阿那曲唑加安慰剂的临床获益率分别为49%和34%，客观缓解率分别为2%和12%。基线生物标志物水平和相对治疗效果之间没有相互作用的证据被发现。没有意想不到的不良事件observed.Conclusion：这个小的随机研究表明，阿那曲唑与吉非替尼相结合，与阿那曲唑加安慰剂相比，在PFS中具有显着的优势，并且该组合是耐受的绝经后妇女与激素受体阳性MBC。可能需要进一步研究表皮生长因子受体抑制剂联合内分泌治疗。临床癌症研究; 16（6）; 1904-14。(C)2010年AACR。
Purpose: This phase II randomized trial evaluated the efficacy and tolerability of anastrozole combined with gefitinib or anastrozole with placebo in women with hormone receptor-positive metastatic breast cancer (MBC).Experimental Design: Postmenopausal women with hormone receptor-positive measurable or evaluable MBC who had not received prior endocrine therapy for this disease stage or who developed metastatic disease during/after adjuvant tamoxifen were eligible. The primary response variable was progression-free survival (PFS) and secondary response variables included clinical benefit rate, objective response rate, overall survival, safety and tolerability, and pharmacokinetics. Tumor biomarker evaluation was an exploratory objective.Results: Forty-three patients were randomized to anastrozole plus gefitinib and 50 patients were randomized to anastrozole plus placebo of a planned total of 174 patients (enrollment was prematurely discontinued due to slow recruitment). PFS for patients receiving the combination of anastrozole and gefitinib was longer than for patients receiving anastrozole plus placebo [hazard ratio (gefitinib/placebo), 0.55; 95% confidence interval, 0.32-0.94; median PFS, 14.7 versus 8.4 months]. The clinical benefit rate was 49% versus 34%, and the objective response rate was 2% versus 12% with anastrozole plus gefitinib and anastrozole plus placebo, respectively. No evidence of interaction between baseline biomarker levels and relative treatment effect was found. No unexpected adverse events were observed.Conclusion: This small randomized study showed that anastrozole in combination with gefitinib is associated with a marked advantage in PFS compared with anastrozole plus placebo, and that the combination was tolerated in postmenopausal women with hormone receptor-positive MBC. Further investigation of epidermal growth factor receptor inhibition in combination with endocrine therapy may be warranted. Clin Cancer Res; 16(6); 1904-14. (C) 2010 AACR.