Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
J Cancer Res Clin Oncol. 2013 Oct;139(10):1691-700. doi: 10.1007/s00432-013-1495-0. Epub 2013 Aug 22.
The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) differs in patients with lung adenocarcinoma harboring EGFR-activating mutations. Although lung adenocarcinoma with EGFR-activating mutations has heterogeneous morphologic features, the predictive role of histologic subtype of lung adenocarcinoma with regard to the effectiveness of EGFR-TKIs in patients with EGFR-activating mutations has not been well defined.
Among 134 postoperative recurrence patients with lung adenocarcinoma harboring EGFR-activating mutation (L858R or exon 19 deletion) treated with EGFR-TKIs, we retrospectively analyzed 61 patients treated with EGFR-TKIs as first-line chemotherapy. All the tumors were classified according to the new histologic classification proposed by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) into the following subtypes: lepidic, papillary, acinar, micropapillary, or solid predominant subtype. We evaluated the correlation between the histologic subtype and the clinical efficacy of EGFR-TKIs.
In overall response rate, adenocarcinoma with solid predominant subtype is significantly worse than with non-solid predominant subtype (61 vs. 88 %, P = 0.03). The median progression-free survival (PFS) and overall survival after EGFR-TKI treatment were significantly shorter for the patients with solid predominant subtype than for those with non-solid predominant subtype (median PFS of 7.7 vs. 13.5 months, P = 0.002, and median OS of 21.5 vs. 31.0 months, P = 0.028).
This study indicated that among patients with lung adenocarcinoma harboring activating EGFR mutations treated with EGFR-TKIs, solid predominant subtype according to IASLC/ATS/ERS classification is a response predictor for EGFR-TKI.
表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKIs)在携带 EGFR 激活突变的肺腺癌患者中的疗效不同。虽然携带 EGFR 激活突变的肺腺癌具有异质性的形态特征,但肺腺癌组织学亚型与 EGFR-TKIs 治疗携带 EGFR 激活突变患者的疗效之间的预测作用尚未得到很好的定义。
在 134 例接受 EGFR-TKIs 治疗的携带 EGFR 激活突变(L858R 或外显子 19 缺失)的肺腺癌术后复发患者中,我们回顾性分析了 61 例接受 EGFR-TKIs 作为一线化疗的患者。所有肿瘤均根据国际肺癌研究协会(IASLC)、美国胸科学会(ATS)和欧洲呼吸学会(ERS)提出的新组织学分类分为以下亚型:贴壁型、乳头状型、腺泡型、微乳头型或实体为主型。我们评估了组织学亚型与 EGFR-TKIs 临床疗效之间的相关性。
在总缓解率方面,实体为主型腺癌明显低于非实体为主型(61% vs. 88%,P = 0.03)。EGFR-TKI 治疗后患者的中位无进展生存期(PFS)和总生存期明显短于非实体为主型(中位 PFS 为 7.7 个月 vs. 13.5 个月,P = 0.002,中位 OS 为 21.5 个月 vs. 31.0 个月,P = 0.028)。
本研究表明,在接受 EGFR-TKIs 治疗的携带激活 EGFR 突变的肺腺癌患者中,根据 IASLC/ATS/ERS 分类的实体为主型是 EGFR-TKI 反应的预测因子。