Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial
Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial
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DOI：
10.1007/s10549-011-1352-2
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发表时间：
2011-04-01
影响因子：
3.8
通讯作者：
Ejlertsen, Bent
中科院分区：
文献类型：
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作者：
Bernsdorf, Mogens;Ingvar, Christian;Ejlertsen, Bent
吉非替尼是一种表皮生长因子受体酪氨酸激酶抑制剂，在乳腺癌中显示出抗增殖和抗肿瘤活性。本研究旨在确定在新辅助表阿霉素和环磷酰胺 (EC) 中添加吉非替尼对肿瘤缓解率的影响。患有单侧、原发性可手术、雌激素受体阴性浸润性乳腺癌（千分之一2厘米）的女性有资格入选。随机患者接受四个周期的新辅助 EC 加 12 周的吉非替尼（每天 250 毫克）或安慰剂。主要终点是病理完全缓解（pCR），次要终点是完全缓解（CR）和总体客观缓解（OR）。 181 名患者被随机分组。在接受吉非替尼治疗的患者中观察到 17% (12/71) 的患者达到 pCR，在接受安慰剂治疗的患者中观察到 12% (9/73) 的患者达到 pCR（差异 4.57%，95% CI -7.19 至 6.33；P = 0.44）。吉非替尼组 (7/71) 和安慰剂组 (7/73) 均有 10% 的患者获得 CR（差异为 0.27%，95% CI -9.6 至 10.2；P = 0.96）。两组之间的 OR（5.96%；95% CI -9.9 至 21.9；P = 0.45）无显着差异。事后亚组分析显示三阴性乳腺癌 (TNBC) 和非 TNBC 肿瘤之间的 pCR 存在显着差异 (P = 0.03)。吉非替尼组中有更多患者出现血液学毒性（P = 0.15）并因不良事件（AE）而停止治疗（9/94 vs. 2/86）。两组的肿瘤缓解率相似。事后观察到 TNBC 的 pCR 率显着高于非 TNBC（独立于治疗）。吉非替尼组中有更多患者因 AE 停止治疗。
Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has shown both anti-proliferative and anti-tumoral activity in breast cancer. This study was designed to determine the effect of adding gefitinib to neoadjuvant epirubicin and cyclophosphamide (EC) on tumor response rates. Women with unilateral, primary operable, estrogen receptor negative invasive breast cancer a parts per thousand yen 2 cm were eligible for inclusion. Randomized patients were to receive four cycles of neoadjuvant EC plus 12 weeks of either gefitinib (250 mg daily) or placebo. Primary endpoint was pathologic complete response (pCR), and secondary endpoints were complete response (CR) and overall objective response (OR). 181 patients were randomized. A pCR was observed in 17% (12/71) of patients treated with gefitinib and in 12% (9/73) of patients treated with placebo (4.57% difference, 95% CI -7.19 to 6.33; P = 0.44). CR was observed in 10% of patients in both the gefitinib (7/71) and the placebo group (7/73) (0.27% difference, 95% CI -9.6 to 10.2; P = 0.96). There was no significant difference in OR (5.96%; 95% CI -9.9 to 21.9; P = 0.45) between the two groups. Post hoc subgroup analysis showed a significant difference in pCR between triple negative breast cancer (TNBC) and non-TNBC tumors (P = 0.03). More patients in the gefitinib arm had hematological toxicity (P = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups. A significantly higher pCR rate was observed post hoc in TNBC versus non-TNBC independent of treatment. More patients in the gefitinib group discontinued treatment because of AE.