期刊
LUNG CANCER
卷 155, 期 -, 页码 20-27出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.lungcan.2021.03.006
关键词
Resistance; Epidermal growth factor receptor mutation; Small cell carcinoma; Transformation; Next-generation sequencing
资金
- Medical Scientific Research Foundation of Zhejiang Province [2019RC027]
- Xisike-Hanson Cancer Research Foundation [Y-HS2019-20]
The study found that TP53 and RB1 mutations were common in patients with SCLC transformation in China, regardless of whether first/second-generation or third-generation EGFR-TKIs were used. After transformation to SCLC, platinum-etoposide was the most common treatment regimen, and anlotinib showed good efficacy in these patients.
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 platinumetoposide 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.
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