Shinno Yuki, Goto Yasushi, Watanabe Sho, Sato Jun, Morita Ryo, Matsumoto Yuji, Murakami Shuji, Kanda Shintaro, Horinouchi Hidehito, Fujiwara Yutaka, Yamamoto Noboru, Ohe Yuichiro
Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
ESMO Open. 2018 Nov 28;3(7):e000399. doi: 10.1136/esmoopen-2018-000399. eCollection 2018.
Epidermal growth factor receptor (EGFR) is one of the most common oncogenes in non-small cell lung cancer (NSCLC). EGFR-tyrosine kinase inhibitor (TKI) and platinum-doublet chemotherapy (PT) are effective regimens in patients with NSCLC harbouring EGFR mutations. Among these patients, progression-free survival (PFS) has been used as a surrogate endpoint; however, it may not correlate with overall survival (OS) due to crossover. Time to failure of strategy (TFS) has been proposed as an alternative endpoint in advanced colorectal cancer clinical trials where multiple effective therapies are provided either in combination or sequentially. Nevertheless, it remains unclear whether TFS is useful in lung cancer trials.
We retrospectively reviewed patients with NSCLC harbouring EGFR mutations who chose a treatment strategy consisting of EGFR-TKI and PT as the initial two regimens at the National Cancer Center Hospital. We evaluated the relationship between PFS and OS and between TFS and OS.
Between May 2005 and April 2015, a total of 374 patients were diagnosed with NSCLC harbouring EGFR mutations. Among them, 158 patients were eligible for analysis. The median PFS, TFS and OS of the patients were 11.2 months (95% CI 9.9 to 12.6), 21.3 months (95% CI 18.6 to 26.2) and 36.6 months (95% CI 32.0 to 41.8), respectively. OS and TFS, but not PFS, were better in patients who received PT then EGFR-TKI compared with those who received the opposite schedule. The non-parametric Spearman's rank correlation coefficients (r) between PFS and OS and between TFS and OS were 0.54 and 0.85, respectively.
This is the first report describing TFS data among patients with NSCLC with EGFR mutations who received EGFR-TKI and PT as the initial two regimens. TFS was acceptable as a surrogate endpoint for OS. Further validation in clinical trials is needed.
表皮生长因子受体（EGFR）是非小细胞肺癌（NSCLC）中最常见的致癌基因之一。EGFR酪氨酸激酶抑制剂（TKI）和铂类双联化疗（PT）是治疗携带EGFR突变的NSCLC患者的有效方案。在这些患者中，无进展生存期（PFS）已被用作替代终点；然而，由于交叉现象，它可能与总生存期（OS）无关。在提供多种联合或序贯有效治疗的晚期结直肠癌临床试验中，已提出策略失败时间（TFS）作为替代终点。然而，TFS在肺癌试验中是否有用仍不清楚。
我们回顾性分析了在国立癌症中心医院选择EGFR-TKI和PT作为初始两种治疗方案的携带EGFR突变的NSCLC患者。我们评估了PFS与OS之间以及TFS与OS之间的关系。
2005年5月至2015年4月期间，共有374例患者被诊断为携带EGFR突变的NSCLC。其中，158例患者符合分析条件。患者的中位PFS、TFS和OS分别为11.2个月（95%CI 9.9至12.6）、21.3个月（95%CI 18.6至26.2）和36.6个月（95%CI 32.0至41.8）。与接受相反治疗顺序的患者相比，先接受PT然后接受EGFR-TKI治疗的患者的OS和TFS更好，但PFS并非如此。PFS与OS之间以及TFS与OS之间的非参数Spearman等级相关系数（r）分别为0.54和0.85。
这是第一份描述接受EGFR-TKI和PT作为初始两种治疗方案的携带EGFR突变的NSCLC患者TFS数据的报告。TFS可作为OS的替代终点。需要在临床试验中进一步验证。
