Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Lung Cancer. 2019 Apr;130:18-24. doi: 10.1016/j.lungcan.2019.01.016. Epub 2019 Jan 31.
Sequential combination of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and chemotherapy has shown greater benefits than either treatment alone in non-small-cell lung cancer (NSCLC). In this follow-up of the ENSURE study, we evaluated progression-free survival (PFS) with first-line erlotinib followed by chemotherapy at progression versus the inverse treatment sequence in 175 Chinese patients with EGFR mutation-positive NSCLC.
Forty-five of the 175 patients included in the follow-up analysis experienced progressive disease (PD). Those with PD on first-line erlotinib (n = 24) received gemcitabine/cisplatin while those who failed first-line chemotherapy (n = 21) received erlotinib until second-line PD. The primary endpoint was PFS in the crossover subpopulation. Post-hoc analysis of survival outcomes was also measured for the overall population of 175 Chinese patients.
Among patients who crossed over at progression, PFS was comparable between those who received second-line erlotinib and those who received second-line chemotherapy (median, 26.3 months and 23.4 months, respectively; P = 0.529). Regardless of the sequence in which the therapies were administered, patients in the crossover treatment subgroup benefited from either second-line therapy after progression with a median overall survival of 51.6 months versus 23.0 months achieved among patients in the non-crossover treatment subgroup. Post-hoc biomarker analyses of Kaplan-Meier survival curves and Cox regression showed that survival benefits with either treatment sequence were similar between patients with circulating free DNA EGFR mutations in exons 19 and 21; however, those with undetectable mutations achieved significantly greater survival benefits.
In advanced EGFR mutation-positive NSCLC, first-line erlotinib followed by chemotherapy at progression demonstrated comparable PFS benefit with the inverse treatment sequence, irrespective of mutation subtype. Utilizing both EGFR-TKIs and chemotherapy, irrespective of the sequence, maximizes survival benefits for patients.
表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKI）与化疗的序贯联合治疗在非小细胞肺癌（NSCLC）中的疗效优于单一治疗。在ENSURE 研究的随访中，我们评估了一线厄洛替尼治疗后进展时换用化疗与相反治疗顺序在 175 例 EGFR 突变阳性 NSCLC 中国患者中的无进展生存期（PFS）。
在随访分析中，有 45 例患者发生进展（PD）。一线厄洛替尼治疗时发生 PD（n=24）的患者接受吉西他滨/顺铂治疗，而一线化疗失败的患者（n=21）接受厄洛替尼直至二线 PD。主要终点是交叉亚组的 PFS。还对 175 例中国患者的总体人群进行了生存结局的事后分析。
在进展时交叉的患者中，二线厄洛替尼和二线化疗的 PFS 无显著差异（中位，分别为 26.3 个月和 23.4 个月；P=0.529）。无论治疗顺序如何，交叉治疗亚组的患者在进展后接受二线治疗均从中获益，总生存的中位时间分别为 51.6 个月和 23.0 个月，而非交叉治疗亚组的患者分别为 23.0 个月和 23.0 个月。Kaplan-Meier 生存曲线和 Cox 回归的事后生物标志物分析显示，在存在 EGFR 外显子 19 和 21 循环游离 DNA 突变的患者中，两种治疗顺序的生存获益相似；然而，那些未检测到突变的患者则获得了显著更大的生存获益。
在晚期 EGFR 突变阳性 NSCLC 中，一线厄洛替尼治疗后进展时换用化疗与相反治疗顺序相比，PFS 获益相似，无论突变亚型如何。无论治疗顺序如何，同时使用 EGFR-TKI 和化疗均可使患者获得最大的生存获益。
