Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030-1439, USA.
Clin Cancer Res. 2010 Mar 15;16(6):1904-14. doi: 10.1158/1078-0432.CCR-09-2282. Epub 2010 Mar 9.
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).
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.
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.
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.
本 II 期随机试验评估了阿那曲唑联合吉非替尼或阿那曲唑联合安慰剂在激素受体阳性转移性乳腺癌（MBC）女性中的疗效和耐受性。
符合条件的患者为绝经后激素受体阳性的可测量或可评估的 MBC 患者，这些患者之前未接受过针对该疾病阶段的内分泌治疗，或在辅助他莫昔芬期间/之后发生转移性疾病。主要反应变量为无进展生存期（PFS），次要反应变量包括临床获益率、客观缓解率、总生存期、安全性和耐受性以及药代动力学。肿瘤生物标志物评估是探索性目标。
43 名患者被随机分配至阿那曲唑联合吉非替尼组，50 名患者被随机分配至阿那曲唑联合安慰剂组，计划入组 174 名患者（由于招募缓慢，提前停止入组）。接受阿那曲唑联合吉非替尼治疗的患者的 PFS 长于接受阿那曲唑联合安慰剂的患者[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 个月对 8.4 个月]。临床获益率分别为 49%和 34%，客观缓解率分别为 2%和 12%。未发现基线生物标志物水平与相对治疗效果之间存在相互作用的证据。未观察到意外的不良事件。
这项小型随机研究表明，与阿那曲唑联合安慰剂相比，阿那曲唑联合吉非替尼治疗可显著延长 PFS，且在绝经后激素受体阳性 MBC 女性中耐受良好。可能需要进一步研究表皮生长因子受体抑制联合内分泌治疗。
