Genomic alterations and clinical outcomes in patients with lung adenocarcinoma with transformation to small cell lung cancer after treatment with EGFR tyrosine kinase inhibitors: A multicenter retrospective study. (May 2021)

• Record Type: Journal Article
• Authors: Wang, Wenxian; Xu, Chunwei; Chen, Huafei; Jia, Jinhao; Wang, Liping; Feng, Huijing; Wang, Hong; Song, Zhengbo; Yang, Nong; Zhang, Yongchang
• Is Part Of: Lung cancer. Volume 155(2021)
• Page Start: 20
• Page End: 27
• Publication Date: 2021-05
• Subjects: Resistance -- Epidermal growth factor receptor mutation -- Small cell carcinoma -- Transformation -- Next-generation sequencing; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2021.03.006
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: The most common mutations identified were TP53 and RB1 in transformation to SCLC. The rates of RB1 and TP53 were similar between first and third-generation TKI treatment. Earlier occurrence of SCLC transformation was associated with poorer prognosis. Anlotinib may be a good treatment choice in transformation to SCLC population. Abstract: Background: Transformation to small cell lung cancer (SCLC) is a resistance mechanism to tyrosine kinase inhibitor (TKI) treatment that develops in lung adenocarcinoma. The genomic and treatment outcomes in these populations have not been comprehensively reported in China. Methods: We performed a retrospective study analyzing patients with advanced non-SCLC (NSCLC) from eight sites who were diagnosed with SCLC transformation after receiving epidermal growth factor receptor (EGFR)-TKI treatment including first/second- or third-generation EGFR-TKIs. We assessed the genomic features and clinical prognosis in these patients with EGFR-mutated lung cancer. Results: Thirty-two eligible patients with EGFR mutations were identified, 25 of whom had sufficient tumor tissues for detection of genes by next-generation sequencing. The median progression free survival (mPFS) for first/second-generation TKIs was 14.0 months. The most common mutations identified in samples with transformation to SCLC were in TP53 (17/25, 68.0 %), RB1 (9/25, 36.0 %), and PIK3CA (3/25, 12.0 %), and the incidence rates of RB1 and TP53 mutations were similar between patients receiving first/second-generation and third-generation TKI treatment. The estimated median time to SCLC transformation was 17.0 months. After SCLC transformation, platinum-etoposide was the most common treatment regimen, and the mPFS after platinum-etoposide treatment was 3.5 months. Anlotinib showed good efficacy in these patients (overall response rate, 66.7 %; mPFS, 6.2 months). The median overall survival after the initial diagnosis of metastatic lung cancer was 34.5 months, and patients with small cell transformation after third-generation TKI treatment had better prognosis than patients with transformation after first/second-generation treatment (49.4 months vs. 20.0 months, P = 0.013). Conclusion: We observed that TP53 and RB1 mutations were common in Chinese patients with SCLC transformation, regardless of whether first/second-generation or third-generation EGFR-TKI treatments were used. Earlier occurrence of small cell transformation after EGFR-TKI treatment was associated with poorer prognosis of patients. After the standard chemotherapy regimens for the management of primary SCLC, anlotinib may be a therapeutic option.