Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, No. 8 Dongdajie, Beijing, 100071, China.
J Cancer Res Clin Oncol. 2014 Mar;140(3):427-33. doi: 10.1007/s00432-014-1582-x. Epub 2014 Jan 9.
It was reported the retreatment of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) may bring benefit to non-small-cell lung cancer (NSCLC) patients who benefited previously. Nevertheless, the treatment order in most of the prior literature was gefitinib (G) to erlotinib (E), and little was known about whether other treatment order may also bring benefit to the patients.
One hundred and twenty NSCLC patients who received EGFR-TKIs treatment twice were enrolled in this study. The safety and effectiveness of the second EGFR-TKIs administration, as well as the influencing factors that contribute to this process, were analyzed retrospectively.
Forty-nine (40.8%) patients were retreated with same kind of EGFR-TKIs: 30 (25%) were G and 19 (15.8%) were E. Seventy-one (59.2%) patients switched to another kind: 55 (45.8%) were G to E and 16 (13.4%) were the reverse. Notably, no differences in clinical benefits were found among the four different treatment orders. For the second administration, the adverse effects of all patients were generally classified as grade I-II and the 1-year survival rate reached 32.5%. The objective response rate, disease control rate, median progression-free survival (PFS), and overall survival was 10.0% (12/120), 52.5% (63/120), 2.3 (95% CI 1.5-3.0) months and 8.0 (95% CI 7.0-8.5) months, respectively. The univariate and multivariate analyses revealed that those patients who benefited from prior EGFR-TKIs were easier to get benefit from the second administration, and the strongest beneficial indicators of the retreatment were PFS of the initial EGFR-TKIs (≥6 months, HR 0.611, 95% CI 0.354-0.901, P = 0.0076) and time interval between the two EGFR-TKIs treatment (≥4 months, HR 0.529, 95% CI 0.328-0.852, P = 0.0088).
Those patients who benefited from prior EGFR-TKIs were easier to get benefit from the second administration. A time interval of ≥4 months may improve the retreatment, but differences in clinical benefit were not found among different treatment orders. If the retrospective result could be validated further in the future, it would be helpful for rational administration of EGFR-TKIs.
据报道，表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）的再治疗可能会给先前受益的非小细胞肺癌（NSCLC）患者带来益处。然而，在大多数先前的文献中，治疗顺序是吉非替尼（G）到厄洛替尼（E），而对于其他治疗顺序是否也能给患者带来益处则知之甚少。
本研究纳入了 120 名接受 EGFR-TKIs 治疗两次的 NSCLC 患者。回顾性分析了第二次 EGFR-TKIs 给药的安全性和有效性，以及影响这一过程的因素。
49 名（40.8%）患者接受同种 EGFR-TKIs 再治疗：30 名（25%）为 G，19 名（15.8%）为 E。71 名（59.2%）患者换用另一种药物：55 名（45.8%）为 G 换 E，16 名（13.4%）为 E 换 G。值得注意的是，四种不同的治疗顺序之间没有发现临床获益的差异。对于第二次给药，所有患者的不良反应一般为 1-2 级，1 年生存率达到 32.5%。客观缓解率、疾病控制率、中位无进展生存期（PFS）和总生存期分别为 10.0%（12/120）、52.5%（63/120）、2.3（95%CI 1.5-3.0）个月和 8.0（95%CI 7.0-8.5）个月。单因素和多因素分析表明，先前接受 EGFR-TKIs 治疗受益的患者更容易从第二次治疗中获益，而初始 EGFR-TKIs 治疗的 PFS（≥6 个月，HR 0.611，95%CI 0.354-0.901，P=0.0076）和两次 EGFR-TKIs 治疗之间的时间间隔（≥4 个月，HR 0.529，95%CI 0.328-0.852，P=0.0088）是再治疗的最强有益指标。
先前接受 EGFR-TKIs 治疗受益的患者更容易从第二次治疗中获益。间隔时间≥4 个月可能会改善再治疗效果，但不同治疗顺序之间没有发现临床获益的差异。如果未来能够进一步验证回顾性结果，将有助于合理应用 EGFR-TKIs。
