Division of Respirology, NTT Medical Center Tokyo, Tokyo, Japan,
Division of Respirology, NTT Medical Center Tokyo, Tokyo, Japan.
Oncology. 2020;98(1):23-28. doi: 10.1159/000502528. Epub 2019 Sep 6.
Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), is effective against EGFR-mutated non-small cell lung carcinoma resistant to first- or second-generation EGFR-TKIs in patients in whom an EGFR T790M mutation has been detected. Detection of the T790M mutation using circulating tumor DNA (ctDNA) is less invasive than a tissue re-biopsy, including a transbronchial lung biopsy; however, the prognostic implications of the T790M mutation in ctDNA have not been fully elucidated.
We retrospectively reviewed the clinical features of non-small cell lung carcinoma patients in whom an EGFR T790M mutation had been detected at our hospital and assessed the clinical outcomes of osimertinib for these patients in terms of detection sites.
An EGFR T790M mutation was detected in 32 non-small cell lung carcinoma patients, of whom 21 (65.6%) underwent osimertinib treatment after detection of the mutation. The mutation was detected using plasma samples in 10 patients (47.6%; liquid biopsy group), while it was detected using tissue samples in 11 patients (52.4%; tissue biopsy group). Liver and bone metastases were more frequently observed in patients in the liquid biopsy group than in the tissue biopsy group (30.0 vs. 0% and 60.0 vs. 18.2%, respectively). The median progression-free survival time was significantly shorter in the liquid biopsy group (132.0 days) than in the tissue biopsy group (682.0 days). The median overall survival time in the liquid biopsy group was 376.0 days, whereas that in the tissue biopsy group was not reached during our observation period.
Non-small cell lung carcinoma patients in whom an EGFR T790M mutation was detected in plasma samples demonstrated a poorer response to osimertinib than those in whom the mutation was detected in tissue specimens.
奥希替尼是第三代表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKI），对检测到 EGFR T790M 突变的、对第一代或第二代 EGFR-TKI 耐药的 EGFR 突变型非小细胞肺癌患者有效。与组织再活检（包括经支气管肺活检）相比，使用循环肿瘤 DNA（ctDNA）检测 T790M 突变的侵入性更小；然而，ctDNA 中 T790M 突变的预后意义尚未完全阐明。
我们回顾性地审查了在我院检测到 EGFR T790M 突变的非小细胞肺癌患者的临床特征，并根据检测部位评估了这些患者使用奥希替尼的临床结局。
32 名非小细胞肺癌患者中检测到 EGFR T790M 突变，其中 21 名（65.6%）在检测到突变后接受了奥希替尼治疗。10 名患者（47.6%；液体活检组）使用血浆样本检测到突变，11 名患者（52.4%；组织活检组）使用组织样本检测到突变。与组织活检组相比，液体活检组患者更常出现肝转移和骨转移（30.0%比 0%和 60.0%比 18.2%）。液体活检组的中位无进展生存期明显短于组织活检组（132.0 天比 682.0 天）。液体活检组的中位总生存期为 376.0 天，而在我们的观察期间，组织活检组未达到中位总生存期。
在血浆样本中检测到 EGFR T790M 突变的非小细胞肺癌患者对奥希替尼的反应不如在组织标本中检测到突变的患者。
