Medical Oncology Service, Vall d'Hebron University Hospital, Barcelona, Spain.
Clin Lung Cancer. 2012 Nov;13(6):432-41. doi: 10.1016/j.cllc.2012.03.004. Epub 2012 May 19.
Pertuzumab, a dimerization inhibitor of human epidermal growth factor receptor 2 (HER2), has demonstrated pharmacodynamic activity, with stable disease in non-small-cell lung cancer. Combining erlotinib and pertuzumab may enhance antitumor activity. This study aimed to establish the recommended dosing of the erlotinib and pertuzumab combination; assess safety, preliminary efficacy, and pharmacokinetics; and analyze biomarkers.
Fifteen patients with stage IIIb/IV non-small-cell lung cancer who failed chemotherapy were recruited. The patients received erlotinib (days -8 to -1), then combination therapy (21-day cycles for 6 cycles). Pertuzumab was given intravenous at 840 mg, then 420 mg once every three weeks, with erlotinib given daily (100 or 150 mg).
No dose-limiting toxicities were observed. Adverse events were generally grade 1/2 and manageable. The objective response rate was 20% (3/15 patients; 2 responders had mutant HER1, 1 responder had wild-type HER1), median overall progression-free survival was 9.3 weeks. High HER1, HER2, and HER3 messenger RNA expression correlated with increased progression-free survival. Combination therapy did not affect erlotinib's pharmacokinetics; however, pertuzumab mean exposures (maximum concentration, 231 mg/L; area under the concentration-time curve from 0 to 21 days, 1780 mg*d/L) were slightly higher than in previous studies.
Combination therapy was well tolerated in patients with good performance status, with encouraging efficacy. A loading dose of pertuzumab 840 mg followed by 420 mg once every three weeks plus daily erlotinib 150 mg appears to be the most appropriate regimen for this combination.
曲妥珠单抗是人表皮生长因子受体 2（HER2）二聚化抑制剂，已显示出药效活性，在非小细胞肺癌中表现为疾病稳定。厄洛替尼和曲妥珠单抗联合使用可能增强抗肿瘤活性。本研究旨在确定厄洛替尼和曲妥珠单抗联合用药的推荐剂量；评估安全性、初步疗效和药代动力学；并分析生物标志物。
招募了 15 名化疗失败的 IIIb/IV 期非小细胞肺癌患者。患者接受厄洛替尼（第-8 天至第-1 天）治疗，然后接受联合治疗（6 个周期，21 天周期）。曲妥珠单抗静脉滴注 840 mg，然后每 3 周给予 420 mg，同时每日给予厄洛替尼（100 或 150 mg）。
未观察到剂量限制毒性。不良反应一般为 1/2 级，且可管理。客观缓解率为 20%（15 例患者中有 3 例；2 例缓解者有突变的 HER1，1 例缓解者有野生型 HER1），中位总无进展生存期为 9.3 周。高 HER1、HER2 和 HER3 信使 RNA 表达与无进展生存期延长相关。联合治疗未影响厄洛替尼的药代动力学；然而，曲妥珠单抗的平均暴露量（最大浓度 231 mg/L；0 至 21 天的浓度-时间曲线下面积 1780 mg*d/L）略高于先前的研究。
在身体状况良好的患者中，联合治疗耐受良好，疗效令人鼓舞。曲妥珠单抗 840 mg 负荷剂量，然后每 3 周给予 420 mg 一次，同时每日给予厄洛替尼 150 mg 似乎是该联合用药的最佳方案。
