Holmes Frankie A, Moy Beverly, Delaloge Suzette, Chia Stephen K L, Ejlertsen Bent, Mansi Janine, Iwata Hiroji, Gnant Michael, Buyse Marc, Barrios Carlos H, Silovski Tajana, Šeparović Robert, Bashford Anna, Zotano Angel Guerrero, Denduluri Neelima, Patt Debra, Gokmen Erhan, Gore Ira, Smith John W, Loibl Sibylle, Masuda Norikazu, Tomašević Zorica, Petráková Katarina, DiPrimeo Daniel, Wong Alvin, Martin Miguel, Chan Arlene
Texas Oncology, P.A., US Oncology Research, Houston, TX, USA.
Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Eur J Cancer. 2023 May;184:48-59. doi: 10.1016/j.ejca.2023.02.002. Epub 2023 Feb 10.
ExteNET showed that neratinib, an irreversible pan-HER tyrosine kinase inhibitor, given for 1 year after trastuzumab-based therapy significantly improved invasive disease-free survival in women with early-stage HER2-positive breast cancer. We report the final analysis of overall survival in ExteNET.
In this international, randomised, double-blind, placebo-controlled, phase 3 trial, women aged 18 years or older with stage 1-3c (amended to stage 2-3c) HER2-positive breast cancer who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab were eligible. Patients were randomly assigned to oral neratinib 240 mg/day or placebo for 1 year. Randomisation was stratified according to hormone receptor (HR) status (HR-positive vs. HR-negative), nodal status (0, 1-3 or 4+), and trastuzumab regimen (sequentially vs. concurrently with chemotherapy). Overall survival was analysed by intention to treat. ExteNET is registered (Clinicaltrials.gov: NCT00878709) and is complete.
Between July 9, 2009, and October 24, 2011, 2840 women received neratinib (n = 1420) or placebo (n = 1420). After a median follow-up of 8.1 (IQR, 7.0-8.8) years, 127 patients (8.9%) in the neratinib group and 137 patients (9.6%) in the placebo group in the intention-to-treat population had died. Eight-year overall survival rates were 90.1% (95% CI 88.3-91.6) with neratinib and 90.2% (95% CI 88.4-91.7) with placebo (stratified hazard ratio 0.95; 95% CI 0.75-1.21; p = 0.6914).
Overall survival in the extended adjuvant setting was comparable for neratinib and placebo after a median follow-up of 8.1 years in women with early-stage HER2-positive breast cancer.
ExteNET研究表明，奈拉替尼是一种不可逆的泛HER酪氨酸激酶抑制剂，在曲妥珠单抗为基础的治疗后给予1年，可显著改善早期HER2阳性乳腺癌女性的无侵袭性疾病生存期。我们报告ExteNET研究中总生存期的最终分析结果。
在这项国际、随机、双盲、安慰剂对照的3期试验中，年龄≥18岁、患有1-3c期（修订为2-3c期）HER2阳性乳腺癌且已完成新辅助和辅助化疗加曲妥珠单抗治疗的女性符合条件。患者被随机分配口服奈拉替尼240mg/天或安慰剂，持续1年。随机分组根据激素受体（HR）状态（HR阳性与HR阴性）、淋巴结状态（0、1-3或4+）以及曲妥珠单抗治疗方案（与化疗序贯或同步）进行分层。总生存期采用意向性分析。ExteNET研究已注册（Clinicaltrials.gov：NCT00878709）且已完成。
在2009年7月9日至2011年10月24日期间，2840名女性接受了奈拉替尼（n = 1420）或安慰剂（n = 1420）治疗。在意向性分析人群中，经过中位8.1（IQR，7.0 - 8.8）年的随访后，奈拉替尼组有127例患者（8.9%）死亡，安慰剂组有137例患者（9.6%）死亡。奈拉替尼组的8年总生存率为90.1%（95%CI 88.3 - 91.6），安慰剂组为90.2%（95%CI 88.4 - 91.7）（分层风险比0.95；95%CI 0.75 - 1.21；p = 0.6914）。
在早期HER2阳性乳腺癌女性中，经过中位8.1年的随访，奈拉替尼和安慰剂在延长辅助治疗中的总生存期相当。
