Endocrine Therapy With or Without Inhibition of Epidermal Growth Factor Receptor and Human Epidermal Growth Factor Receptor 2: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Fulvestrant With or Without Lapatinib for Postmenopausal Women With Hormone Receptor-Positive Advanced Breast Cancer-CALGB 40302 (Alliance)
Endocrine Therapy With or Without Inhibition of Epidermal Growth Factor Receptor and Human Epidermal Growth Factor Receptor 2: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Fulvestrant With or Without Lapatinib for Postmenopausal Women With Hormone Receptor-Positive Advanced Breast Cancer-CALGB 40302 (Alliance)
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DOI：
10.1200/jco.2014.56.7941
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发表时间：
2014-12-10
影响因子：
45.3
通讯作者：
Hudis, Clifford A.
中科院分区：
文献类型：
--
作者：
Burstein, Harold J.;Cirrincione, Constance T.;Hudis, Clifford A.
PurposeCALGB 40302试图确定拉帕替尼是否会改善女性激素受体阳性转移性乳腺癌治疗与fulvestrant.Patients和MethodsEligible妇女无进展生存期（PFS）雌激素受体阳性和/或孕激素受体阳性肿瘤，无论人表皮生长因子受体2（HER 2）的状态，和以前的芳香化酶抑制剂治疗。患者在第1天接受氟维司群500 mg肌内注射，随后在第15天和第28天接受250 mg，此后每4周一次，以及拉帕替尼1，500 mg或安慰剂每日一次。这项研究计划增加324例患者，并与拉帕替尼从5至7.5 months.ResultsAt第三次计划的中期分析，徒劳的边界被越过，数据和安全监测委员会建议关闭研究，已累计295例患者的50%改善。最终分析时，PFS无差异（安慰剂与拉帕替尼的风险比[HR]为1.04; 95% CI为0.82 - 1.33; P = 0.37）;氟维司群+拉帕替尼的中位PFS为4.7个月，氟维司群+安慰剂为3.8个月。总生存期（OS）无差异（HR，0.91; 95% CI，0.68 - 1.21; P = 0.25）。对于HER 2正常肿瘤，各治疗组的中位PFS无差异（4.1 vs 3.8个月）。对于HER 2阳性肿瘤，拉帕替尼与较长的中位PFS（5.9 vs 3.3个月）相关，但HER 2状态的差异治疗效果不显著（P = 0.53）。最常见的毒性是腹泻，疲劳，皮疹与lapatinib.Conclusionadding lapatinib氟维司群不改善PFS或OS在晚期ER阳性乳腺癌，是更有毒。(C)2014年美国临床肿瘤学会
PurposeCALGB 40302 sought to determine whether lapatinib would improve progression-free survival (PFS) among women with hormone receptor-positive metastatic breast cancer treated with fulvestrant.Patients and MethodsEligible women had estrogen receptor-positive and/or progesterone receptor-positive tumors, regardless of human epidermal growth factor receptor 2 (HER2) status, and prior aromatase inhibitor treatment. Patients received fulvestrant 500 mg intramuscularly on day 1, followed by 250 mg on days 15 and 28 and every 4 weeks thereafter, and either lapatinib 1,500 mg or placebo daily. The study planned to accrue 324 patients and was powered for a 50% improvement in PFS with lapatinib from 5 to 7.5 months.ResultsAt the third planned interim analysis, the futility boundary was crossed, and the data and safety monitoring board recommend study closure, having accrued 295 patients. At the final analysis, there was no difference in PFS (hazard ratio [HR] of placebo to lapatinib, 1.04; 95% CI, 0.82 to 1.33; P = .37); median PFS was 4.7 months for fulvestrant plus lapatinib versus 3.8 months for fulvestrant plus placebo. There was no difference in overall survival (OS) (HR, 0.91; 95% CI, 0.68 to 1.21; P = .25). For HER2-normal tumors, median PFS did not differ by treatment arm (4.1 v 3.8 months). For HER2-positive tumors, lapatinib was associated with longer median PFS (5.9 v 3.3 months), but the differential treatment effect by HER2 status was not significant (P = .53). The most frequent toxicities were diarrhea, fatigue, and rash associated with lapatinib.ConclusionAdding lapatinib to fulvestrant does not improve PFS or OS in advanced ER-positive breast cancer and is more toxic. (C) 2014 by American Society of Clinical Oncology