Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
Lung Cancer. 2013 Nov;82(2):299-304. doi: 10.1016/j.lungcan.2013.08.009. Epub 2013 Aug 21.
Gefitinib treatment results in considerably better progression-free survival compared with that of platinum doublets in the first line treatment of nonsmall-cell lung cancer (NSCLC) carrying an activating epidermal growth factor receptor (EGFR) mutation. Some patients who respond to gefitinib have an overall survival (OS) of more than 5 years, whereas other initial responders do less well. Although there has been considerable effort made to elucidate the mechanisms of acquired resistance, there have only been a few studies that addressed the effect of clinical backgrounds and treatment histories on the survival of the patients who had responded to an EGFR-tyrosine kinase inhibitor (TKI). In this study, we especially focused on the clinical benefit of EGFR-TKI administration after progression.
We retrospectively analyzed consecutive patients with advanced NSCLC who were diagnosed before October 2010, treated with gefitinib after July 2002, and responded to it. The primary objective of this study was to evaluate how clinical backgrounds and treatment histories influence survival of the patients who respond to gefitinib. The secondary objectives were to evaluate the safety of long-term gefitinib use and to establish the optimal treatment sequence using a dynamic treatment regimen analysis (DTRA).
A total of 335 patients were recruited. Twenty-eight (8.4%) patients survived more than 5 years. Sixty-five and 93 patients received gefitinib as rechallenge and beyond progressive disease (BPD), respectively. A statistically significant difference in OS was observed between the patients who underwent gefitinib rechallenge and those who did not rechallenge (median: 1272 days vs. 774 days; p < 0.001), a result supported by a DTRA. Patients treated with gefitinib BPD also showed a tendency of longer survival.
Gefitinib rechallenge and BPD played a central role in long term survival of the patients who initially responded to gefitinib.
吉非替尼治疗与铂类双药联合化疗相比,可显著改善携带激活表皮生长因子受体(EGFR)突变的非小细胞肺癌(NSCLC)患者的无进展生存期。一些对吉非替尼有反应的患者总生存期(OS)超过 5 年,而其他初始反应者则效果不佳。尽管已经做了大量努力来阐明获得性耐药的机制,但只有少数研究探讨了临床背景和治疗史对 EGFR 酪氨酸激酶抑制剂(TKI)治疗后有反应的患者生存的影响。在这项研究中,我们特别关注 EGFR-TKI 治疗进展后的临床获益。
我们回顾性分析了 2010 年 10 月前诊断、2002 年 7 月后接受吉非替尼治疗且有反应的晚期 NSCLC 连续患者。本研究的主要目的是评估临床背景和治疗史如何影响对吉非替尼有反应的患者的生存。次要目的是评估长期使用吉非替尼的安全性,并使用动态治疗方案分析(DTRA)建立最佳治疗顺序。
共纳入 335 例患者。28 例(8.4%)患者存活时间超过 5 年。65 例和 93 例患者分别接受吉非替尼再挑战和 beyond progressive disease(BPD)治疗。接受吉非替尼再挑战的患者与未再挑战的患者的 OS 差异具有统计学意义(中位:1272 天比 774 天;p < 0.001),这一结果得到了 DTRA 的支持。接受 BPD 治疗的患者也显示出生存时间延长的趋势。
吉非替尼再挑战和 BPD 在初始对吉非替尼有反应的患者的长期生存中起着核心作用。