Sarosi Veronika, Losonczy Gyorgy, Francovszky Eva, Tolnay Edina, Torok Szilvia, Galffy Gabriella, Hegedus Balazs, Dome Balazs, Ostoros Gyula
Department of Respiratory Medicine, I. Internal Medicine, Medical University, Ifjúság út 13, 7624 Pécs, Hungary.
Department of Pulmonology, Semmelweis University, Diósárok utca 1/C, 1125 Budapest, Hungary.
Lung Cancer. 2014 Oct;86(1):54-8. doi: 10.1016/j.lungcan.2014.07.011. Epub 2014 Jul 27.
Erlotinib is an epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI), used for the treatment of non-small cell lung cancer. As the clinical significance of KRAS mutational status has not yet been clearly determined in this setting, our aim was to investigate the efficacy of erlotinib in advanced KRAS mutation-negative lung adenocarcinoma patients.
MOTIVATE is an open-label, multicenter, observational trial with Tarceva(®) (erlotinib) monotherapy. Enrolled patients with advanced (stage IIIB/IV) KRAS wild type (WT) lung adenocarcinoma refractory to one or two courses of prior chemotherapy were treated with erlotinib at 150mg/day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and best tumor response rate (RR).
In total, 327 patients were included. Median PFS and OS were 3.3 and 14.4 months, respectively. Three patients (1.2%) had complete response, 51 patients (20.2%) had partial response and 123 patients (48.8%) had SD. Significantly longer median PFS and OS were observed in Eastern Oncology Cooperative Group Performance Status (ECOG PS) 0-1 patients, as compared to ECOG PS 2-3 patients. The longest median OS (20.5 months) was found in patients with ECOG PS 0-1 who received erlotinib as a second-line therapy. There was no difference in median OS in cohorts stratified to disease stage and smoking status. Female patients had both longer median PFS and OS. Disease control rate was 70.2%. Our results suggest that erlotinib represents a valid treatment option for patients with KRAS WT lung adenocarcinoma and, moreover, that KRAS mutation analysis could help to identify clinically relevant subgroups of NSCLC patients that may benefit from EGFR-TKI therapy.
厄洛替尼是一种表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI），用于治疗非小细胞肺癌。由于在这种情况下KRAS突变状态的临床意义尚未明确确定，我们的目的是研究厄洛替尼在晚期KRAS突变阴性肺腺癌患者中的疗效。
MOTIVATE是一项使用特罗凯（®）（厄洛替尼）单药治疗的开放标签、多中心观察性试验。纳入的晚期（IIIB/IV期）KRAS野生型（WT）肺腺癌患者，对一或两个疗程的先前化疗耐药，接受厄洛替尼治疗，剂量为每日150mg。主要终点是无进展生存期（PFS）。次要终点是总生存期（OS）和最佳肿瘤缓解率（RR）。
共纳入327例患者。中位PFS和OS分别为3.3个月和14.4个月。3例患者（1.2%）完全缓解，51例患者（20.2%）部分缓解，123例患者（48.8%）疾病稳定。与东部肿瘤协作组体能状态（ECOG PS）2-3级患者相比，ECOG PS 0-1级患者的中位PFS和OS显著更长。ECOG PS 0-1级且接受厄洛替尼作为二线治疗的患者中位OS最长（20.5个月）。按疾病分期和吸烟状态分层的队列中，中位OS无差异。女性患者的中位PFS和OS均更长。疾病控制率为70.2%。我们的结果表明，厄洛替尼是KRAS WT肺腺癌患者的一种有效治疗选择，此外，KRAS突变分析有助于识别可能从EGFR-TKI治疗中获益的非小细胞肺癌患者的临床相关亚组。
