Karen A. Gelmon, David G. Huntsman, and Samuel Aparicio, British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver; Susan L. Ellard, British Columbia Cancer Agency, Cancer Centre for the Southern Interior, Kelowna, British Columbia; Julie Lemieux, Centre Hospitalier Affilié Hopital Du St Sacrement, Quebec City, Quebec; Lois E. Shepherd, Dora Nomikos, Judith-Anne W. Chapman, and Wendy R. Parulekar, NCIC Clinical Trials Group, Queen's University, Kingston; Susan Dent, Ottawa Health Research Institute, Ottawa; Kathleen I. Pritchard, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto; Timothy J. Whelan, Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, Ontario; Katia Tonkin, Cross Cancer Institute, Edmonton, Alberta, Canada; Frances M. Boyle, Patricia Ritchie Centre for Cancer Care and Research, Mater Hospital, North Sydney, New South Wales, Australia; Bella Kaufman, Sheba Medical Centre, Tel Hashomer; Shulamith Rizel, Rabin Medical Center, Petach Tikva, Israel; Alexey Manikhas, City Clinical Oncological Dispensery, St Petersburg; Sergei Tjulandin, Russian Cancer Research Center, Moscow; Rustem Khasanov, Clinical Oncology Dispensary, Kazan, Russia; Angelo Di Leo, Sandro Pitgliani Medical Oncology Unit, Prato, Italy; Miguel Martin, Servicio Oncologia Hospital Gregorio Marañon, Madrid, Spain; Lee S. Schwartzberg, West Clinic, Memphis, TN; Arnd Nusch, Praxis, Velbert, Germany; Robert E. Coleman, Weston Park Hospital, Cancer Research Centre, Sheffield, United Kingdom; Hirofumi Mukai, National Cancer Center Hospital East, Kashiwa-shi, Japan; Anne P. Connor, GlaxoSmithKline, Collegeville, PA; and Sergio L. Santillana, GlaxoSmithKline, Rio de Janeiro, Brazil.
J Clin Oncol. 2015 May 10;33(14):1574-83. doi: 10.1200/JCO.2014.56.9590. Epub 2015 Mar 16.
The efficacy of lapatinib versus trastuzumab combined with taxanes in the first-line setting of human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (BC) is unknown.
The MA.31 trial compared a combination of first-line anti-HER2 therapy (lapatinib or trastuzumab) and taxane therapy for 24 weeks, followed by the same anti-HER2 monotherapy until progression. Stratification was by prior (neo)adjuvant anti-HER2 therapy, prior (neo)adjuvant taxane, planned taxane, and liver metastases. The primary end point was intention-to-treat (ITT) progression-free survival (PFS), defined as time from random assignment to progression by RECIST (version 1.0) criteria, or death for patients with locally assessed HER2-positive tumors. The primary test statistic was a stratified log-rank test for noninferiority. PFS was also assessed for patients with centrally confirmed HER2-positive tumors.
From July 17, 2008, to December 1, 2011, 652 patients were accrued from 21 countries, resulting in 537 patients with centrally confirmed HER2-positive tumors. Median follow-up was 21.5 months. Median ITT PFS was 9.0 months with lapatinib and 11.3 months with trastuzumab. By ITT analysis, PFS was inferior for lapatinib compared with trastuzumab, with a stratified hazard ratio (HR) of 1.37 (95% CI, 1.13 to 1.65; P = .001). In patients with centrally confirmed HER2-positive tumors, median PFS was 9.1 months with lapatinib and 13.6 months with trastuzumab (HR, 1.48; 95% CI, 1.20 to 1.83; P < .001). More grade 3 or 4 diarrhea and rash were observed with lapatinib (P < .001). PFS results were supported by the secondary end point of overall survival, with an ITT HR of 1.28 (95% CI, 0.95 to 1.72; P = .11); in patients with centrally confirmed HER2-positive tumors, the HR was 1.47 (95% CI, 1.03 to 2.09; P = .03).
As first-line therapy for HER2-positive metastatic BC, lapatinib combined with taxane was associated with shorter PFS and more toxicity compared with trastuzumab combined with taxane.
曲妥珠单抗联合紫杉烷类药物作为人表皮生长因子受体 2（HER2）阳性转移性乳腺癌（BC）一线治疗的疗效尚不清楚。
MA.31 试验比较了一线抗 HER2 治疗（拉帕替尼或曲妥珠单抗）联合紫杉烷类药物治疗 24 周，然后继续使用相同的抗 HER2 单药治疗直至进展。分层因素包括既往（新）辅助抗 HER2 治疗、既往（新）辅助紫杉烷类药物、计划使用紫杉烷类药物和肝转移。主要终点为意向治疗（ITT）无进展生存期（PFS），定义为根据 RECIST（版本 1.0）标准从随机分组到进展或局部评估 HER2 阳性肿瘤患者死亡的时间。主要检验统计量为非劣效性分层对数秩检验。还评估了经中心确认的 HER2 阳性肿瘤患者的 PFS。
从 2008 年 7 月 17 日至 2011 年 12 月 1 日，从 21 个国家共入组了 652 例患者，其中 537 例患者经中心确认的 HER2 阳性肿瘤。中位随访时间为 21.5 个月。ITT PFS 中位值为拉帕替尼组 9.0 个月，曲妥珠单抗组 11.3 个月。ITT 分析显示，与曲妥珠单抗相比，拉帕替尼的 PFS 更差，分层风险比（HR）为 1.37（95%CI，1.13 至 1.65；P=0.001）。在经中心确认的 HER2 阳性肿瘤患者中，拉帕替尼组中位 PFS 为 9.1 个月，曲妥珠单抗组为 13.6 个月（HR，1.48；95%CI，1.20 至 1.83；P<0.001）。拉帕替尼组更常见 3 级或 4 级腹泻和皮疹（P<0.001）。PFS 结果也支持总生存期的次要终点，ITT HR 为 1.28（95%CI，0.95 至 1.72；P=0.11）；在经中心确认的 HER2 阳性肿瘤患者中，HR 为 1.47（95%CI，1.03 至 2.09；P=0.03）。
作为 HER2 阳性转移性 BC 的一线治疗，与曲妥珠单抗联合紫杉烷类药物相比，拉帕替尼联合紫杉烷类药物治疗的 PFS 更短，毒性更大。
