Department of Respiratory Medicine, National Center for Global Health and Medicine, Tokyo, Japan.
Medicine (Baltimore). 2022 Aug 12;101(32):e29682. doi: 10.1097/MD.0000000000029682.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely used for the treatment of EGFR mutation positive advanced nonsmall cell lung cancer (NSCLC); however, acquired resistance is known to develop during these treatments. Among these mechanisms, histological transformation is seldom encountered. Although platinum based chemotherapy has been reported to be effective in the treatment of patients with small cell lung cancer transformation, there is a lack of information on the treatment of patients with squamous cell carcinoma (SQ) transformation.
An 80-year-old nonsmoking woman was referred to our hospital because of an abnormal shadow on her chest radiograph. Diagnostic bronchoscopy was performed and pathological examination revealed adenocarcinoma. Mutation analysis of the EGFR gene revealed deletion of E746-A750 in exon 19. She refused both surgical treatment and radiation therapy, and preferred periodic radiologic follow-up. Unfortunately, approximately a year and a half after the initial diagnosis, the primary lesion enlarged, and many pleural nodules were newly detected (clinically T4N2M1a, stage IVA).
Based on EGFR mutation analysis, a reduced dose of daily erlotinib was prescribed, which achieved a partial response and 34 months of progression-free survival (PFS). A repeated biopsy with an endobronchial cryoprobe was performed on the enlarged primary lesion. Pathological examination revealed SQ harboring an identical EGFR mutation with a secondary EGFR T790M mutation. Osimertinib 80 mg once a day was started as second line therapy, which resulted in 8 months of PFS and 15 months of survival.
The literature review and our report suggest that osimertinib is a promising treatment for NSCLC regardless of histology if T790M is present as an acquired mutation.
表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）广泛用于治疗 EGFR 突变阳性的晚期非小细胞肺癌（NSCLC）；然而，已知在这些治疗中会产生获得性耐药。在这些机制中，组织学转化很少见。虽然已有报道称铂类化疗对小细胞肺癌转化患者有效，但对于鳞状细胞癌（SQ）转化患者的治疗信息却很少。
一位 80 岁的不吸烟女性因胸部 X 线片上出现异常阴影而被转至我院。进行了诊断性支气管镜检查，病理检查显示为腺癌。EGFR 基因的突变分析显示外显子 19 缺失 E746-A750。她拒绝手术和放疗，更喜欢定期进行影像学随访。不幸的是，在最初诊断后大约一年半，原发病灶增大，并且新发现了许多胸膜结节（临床 T4N2M1a，IV 期 A 类）。
基于 EGFR 突变分析，每天给予厄洛替尼的低剂量治疗，达到部分缓解和 34 个月的无进展生存期（PFS）。对增大的原发病灶进行了支气管内冷冻探针重复活检。病理检查显示 SQ 存在与相同 EGFR 突变的二次 EGFR T790M 突变。开始二线治疗，每天口服奥希替尼 80mg，结果 PFS 为 8 个月，生存时间为 15 个月。
文献复习和我们的报告表明，如果存在获得性 T790M 突变，奥希替尼是一种有前途的治疗非小细胞肺癌的药物，无论组织学类型如何。
