Department of Respiratory Medicine, Okayama University Hospital, 2-5-1, Shikata-cho, Kitaku, Okayama, 700-8558, Japan.
Cancer Chemother Pharmacol. 2014 May;73(5):943-50. doi: 10.1007/s00280-014-2425-9. Epub 2014 Mar 16.
Early administration of both epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) monotherapy and cytotoxic chemotherapy is crucial for non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. We investigated the effect of first-line administration of these therapies on subsequent therapy in NSCLC patients.
This study enrolled 63 consecutive patients with advanced EGFR-mutant NSCLC and good performance status (PS) and who underwent first-line EGFR-TKI therapy or standard cytotoxic chemotherapy and then had progressive disease, from 2007 to 2011. The ability of each patient to receive the other therapy after first-line treatment failure was assessed.
In the first-line setting, 23 and 40 patients received EGFR-TKI therapy and cytotoxic chemotherapy, respectively. At relapse, the EGFR-TKI therapy group showed more frequent PS deterioration (p = 0.042) and greater likelihood of symptomatic central nervous system (CNS) relapse (p = 0.093) compared with the cytotoxic chemotherapy group. Nine (39 %) of 23 patients initially receiving EGFR-TKI therapy could not receive standard cytotoxic therapy after progression mainly due to symptomatic CNS relapse. Only one (3 %) of 40 initially treated with cytotoxic chemotherapy failed to receive subsequent EGFR-TKI therapy (p < 0.001). Multivariate analysis revealed a correlation between the first-line therapy and the failure to switch to the other therapy after disease progression (OR 48.605, p = 0.005).
In this study, patients who could not receive both EGFR-TKI therapy and cytotoxic chemotherapy in the early-line setting were included more in the first-line EGFR-TKI group, suggesting a potential risk associated with missing the timing of administration of subsequent therapy. Further investigation is warranted to detect their pretreatment clinical or molecular characteristics for development of a new treatment strategy specific for such subpopulation.
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）单药治疗和细胞毒化疗的早期应用对 EGFR 突变的非小细胞肺癌（NSCLC）患者至关重要。我们研究了一线治疗这些疗法对 NSCLC 患者后续治疗的影响。
本研究纳入了 2007 年至 2011 年期间 63 例接受一线 EGFR-TKI 治疗或标准细胞毒化疗且病情进展的 EGFR 突变型晚期 NSCLC 患者，这些患者具有良好的体能状态（PS）。评估每位患者在一线治疗失败后接受另一种治疗的能力。
在一线治疗中，分别有 23 例和 40 例患者接受了 EGFR-TKI 治疗和细胞毒化疗。在复发时，与细胞毒化疗组相比，EGFR-TKI 治疗组 PS 恶化更频繁（p = 0.042），且有症状中枢神经系统（CNS）复发的可能性更大（p = 0.093）。23 例最初接受 EGFR-TKI 治疗的患者中，有 9 例（39%）因有症状的 CNS 复发而无法接受标准细胞毒治疗。40 例最初接受细胞毒化疗的患者中，仅有 1 例（3%）因无法接受后续 EGFR-TKI 治疗（p < 0.001）。多变量分析显示，一线治疗与疾病进展后无法转换为另一种治疗之间存在相关性（OR 48.605，p = 0.005）。
在这项研究中，在一线治疗中无法同时接受 EGFR-TKI 治疗和细胞毒化疗的患者更多地被纳入一线 EGFR-TKI 组，这表明错过了后续治疗的时机可能存在潜在风险。需要进一步研究以检测其治疗前的临床或分子特征，为这一亚群制定新的治疗策略。
