Xavier Pivot, Centre Hospitalier Universitaire, Hôpital Jean Minjoz, Besançon, France; Alexey Manikhas, St Petersburg City Oncology Dispensary; Vladimir Semiglazov, Petrov Research Institute of Oncology, St Petersburg, Russian Federation; Bogdan Żurawski, Franciszek Lukaszczyk Oncology Center, Bydgoszcz; Ewa Chmielowska, Centrum Onkologii im. Prof Franciszka Lukaszczyka Oddzial Kliniczny Onkologii, Bydgoszcz, and Uniwersytet Mikolaja Kopernika Torun, Torun; Boguslawa Karaszewska, Przychodnia Lekarska KOMED, ul Wojska Polskiego 6, Konin, Poland; Rozenn Allerton, The Royal Wolverhampton Hospitals National Health Service Trust, Wolverhampton; Stephen Chan, Nottingham University Hospital, Nottingham; Roma Parikh and Fareha Nagi, GlaxoSmithKline, Uxbridge, United Kingdom; Alessandra Fabi, "Regina Elena" National Cancer Institute, Rome; Paolo Bidoli, Azienda Ospedaliera San Gerardo di Monza U.O. Oncologia Medica, Monza, Lombardia; Stefania Gori, Azienda Ospedaliera di Perugia, Ospedale S. Maria della Misericordia, Struttura Complessa di Oncologia Medica, Perugia, Umbria, and Azienda Ospedaliera Sacro Cuore-Don Calabria-Negrar, Negrar, Verona, Italy; Eva Ciruelos, Hospital Universitario 12 de Octubre, Madrid, Spain; Magdolna Dank, SE Radiológiai és Onkoterápiás Klinika; Lajos Hornyak, Veszprém Megyei Csolnoky Ferenc Kórház, Onkológiai Osztály, Budapest, Hungary; Sara Margolin, Karolinska University Hospital, Stockholm, Sweden; Arnd Nusch, Gem Praxis Drs Nusch, Kalhori und Langer, Friedrichstr, Velbert, Germany; and Michelle DeSilvio, Sergio Santillana, and Ramona F. Swaby, GlaxoSmithKline, Collegeville, PA.
J Clin Oncol. 2015 May 10;33(14):1564-73. doi: 10.1200/JCO.2014.57.1794. Epub 2015 Jan 20.
PURPOSE: CEREBEL compared the incidence of CNS metastases as first site of relapse in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer receiving lapatinib-capecitabine or trastuzumab-capecitabine. PATIENTS AND METHODS: Patients without baseline CNS metastases were randomly assigned (1:1) to receive lapatinib-capecitabine (lapatinib 1,250 mg per day; capecitabine 2,000 mg/m(2) per day on days 1 to 14 every 21 days) or trastuzumab-capecitabine (trastuzumab loading dose of 8 mg/kg followed by an infusion of 6 mg/kg every 3 weeks; capecitabine 2,500 mg/m(2) per day on days 1 to 14 every 21 days). The primary end point was incidence of CNS metastases as first site of relapse. Secondary end points included progression-free survival (PFS) and overall survival (OS). RESULTS: The study was terminated early with 540 enrolled patients (271 received lapatinib-capecitabine, and 269 received trastuzumab-capecitabine). Incidence of CNS metastases as first site of relapse was 3% (eight of 251 patients) for lapatinib-capecitabine and 5% (12 of 250 patients) for trastuzumab-capecitabine (treatment differences, -1.6%; 95% CI, -2% to 5%; P = .360). PFS and OS were longer with trastuzumab-capecitabine versus lapatinib-capecitabine (hazard ratio [HR] for PFS, 1.30; 95% CI, 1.04 to 1.64; HR for OS, 1.34; 95% CI, 0.95 to 1.64). Serious adverse events were reported in 13% (34 of 269 patients) and 17% (45 of 267 patients) of patients in the lapatinib-capecitabine and trastuzumab-capecitabine arms, respectively. CONCLUSION: CEREBEL is inconclusive for the primary end point, and no difference was detected between lapatinb-capecitabine and trastuzumab-capecitabine for the incidence of CNS metastases. A better outcome was observed with trastuzumab-capecitabine in the overall population. However, lapatinib-capecitabine efficacy may have been affected by previous exposure to a trastuzumab regimen and/or when treatment was given as first- or second-line therapy in the metastatic setting.
目的：CEREBEI 比较了曲妥珠单抗-卡培他滨或拉帕替尼-卡培他滨治疗人表皮生长因子受体 2 阳性转移性乳腺癌患者中，作为复发的初始部位的中枢神经系统转移的发生率。
方法：无基线中枢神经系统转移的患者按 1:1 比例随机分配（lapatinib 组：每天 1250mg；capecitabine 组：每天 2000mg/m2，第 1 天至第 14 天，每 21 天 1 次）接受拉帕替尼-卡培他滨或曲妥珠单抗-卡培他滨治疗。主要终点是作为复发的初始部位的中枢神经系统转移的发生率。次要终点包括无进展生存期（PFS）和总生存期（OS）。
结果：这项研究因入组 540 例患者（lapatinib 组 271 例，曲妥珠单抗-卡培他滨组 269 例）而提前终止。lapatinib 组中枢神经系统转移的发生率为 3%（251 例中有 8 例），曲妥珠单抗-卡培他滨组为 5%（250 例中有 12 例）（治疗差异，-1.6%；95%CI，-2%至 5%；P=.360）。曲妥珠单抗-卡培他滨组的 PFS 和 OS 长于拉帕替尼-卡培他滨组（PFS 的 HR 为 1.30；95%CI，1.04 至 1.64；OS 的 HR 为 1.34；95%CI，0.95 至 1.64）。lapatinib 组和曲妥珠单抗-卡培他滨组分别有 13%（34/269 例）和 17%（45/267 例）的患者发生严重不良事件。
结论：CEREBEI 对主要终点的结论不确定，与拉帕替尼-卡培他滨相比，曲妥珠单抗-卡培他滨在中枢神经系统转移的发生率上无差异。在总体人群中，曲妥珠单抗-卡培他滨的疗效更好。然而，拉帕替尼-卡培他滨的疗效可能受到先前曲妥珠单抗方案暴露的影响，以及在转移性疾病中作为一线或二线治疗时的疗效。
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