Geyer Charles E, Forster John, Lindquist Deborah, Chan Stephen, Romieu C Gilles, Pienkowski Tadeusz, Jagiello-Gruszfeld Agnieszka, Crown John, Chan Arlene, Kaufman Bella, Skarlos Dimosthenis, Campone Mario, Davidson Neville, Berger Mark, Oliva Cristina, Rubin Stephen D, Stein Steven, Cameron David
Allegheny Cancer Center, Allegheny General Hospital, Pittsburgh, PA 15212, USA.
N Engl J Med. 2006 Dec 28;355(26):2733-43. doi: 10.1056/NEJMoa064320.
Lapatinib, a tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 (HER2, also referred to as HER2/neu) and epidermal growth factor receptor (EGFR), is active in combination with capecitabine in women with HER2-positive metastatic breast cancer that has progressed after trastuzumab-based therapy. In this trial, we compared lapatinib plus capecitabine with capecitabine alone in such patients.
Women with HER2-positive, locally advanced or metastatic breast cancer that had progressed after treatment with regimens that included an anthracycline, a taxane, and trastuzumab were randomly assigned to receive either combination therapy (lapatinib at a dose of 1250 mg per day continuously plus capecitabine at a dose of 2000 mg per square meter of body-surface area on days 1 through 14 of a 21-day cycle) or monotherapy (capecitabine alone at a dose of 2500 mg per square meter on days 1 through 14 of a 21-day cycle). The primary end point was time to progression, based on an evaluation by independent reviewers under blinded conditions.
The interim analysis of time to progression met specified criteria for early reporting on the basis of superiority in the combination-therapy group. The hazard ratio for the independently assessed time to progression was 0.49 (95% confidence interval, 0.34 to 0.71; P<0.001), with 49 events in the combination-therapy group and 72 events in the monotherapy group. The median time to progression was 8.4 months in the combination-therapy group as compared with 4.4 months in the monotherapy group. This improvement was achieved without an increase in serious toxic effects or symptomatic cardiac events.
Lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline, a taxane, and trastuzumab. (ClinicalTrials.gov number, NCT00078572 [ClinicalTrials.gov].).
拉帕替尼是一种人表皮生长因子受体2（HER2，也称为HER2/neu）和表皮生长因子受体（EGFR）的酪氨酸激酶抑制剂，与卡培他滨联合使用时，对接受过曲妥珠单抗治疗后病情进展的HER2阳性转移性乳腺癌女性患者具有活性。在本试验中，我们比较了拉帕替尼加卡培他滨与单独使用卡培他滨在这类患者中的疗效。
HER2阳性、局部晚期或转移性乳腺癌女性患者，在接受包含蒽环类、紫杉烷类和曲妥珠单抗的治疗方案后病情进展，被随机分配接受联合治疗（拉帕替尼每日剂量1250mg持续服用，加卡培他滨每日剂量2000mg每平方米体表面积，在21天周期的第1至14天服用）或单药治疗（单独使用卡培他滨，每日剂量2500mg每平方米体表面积，在21天周期的第1至14天服用）。主要终点是基于独立审评员在盲态下的评估得出的疾病进展时间。
疾病进展时间的中期分析达到了基于联合治疗组优越性进行早期报告的指定标准。独立评估的疾病进展时间的风险比为0.49（95%置信区间，0.34至0.71；P<0.001），联合治疗组有49例事件，单药治疗组有72例事件。联合治疗组的疾病进展中位时间为8.4个月，而单药治疗组为4.4个月。这种改善在未增加严重毒性作用或有症状的心脏事件的情况下实现。
对于接受过包含蒽环类、紫杉烷类和曲妥珠单抗的治疗方案后病情进展的HER2阳性晚期乳腺癌女性患者，拉帕替尼加卡培他滨优于单独使用卡培他滨。（临床试验注册号，NCT00078572 [ClinicalTrials.gov]。）
