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

•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 tran...

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Veröffentlicht in:Lung cancer (Amsterdam, Netherlands) Netherlands), 2021-05, Vol.155, p.20-27
Hauptverfasser: Wang, Wenxian, Xu, Chunwei, Chen, Huafei, Jia, Jinhao, Wang, Liping, Feng, Huijing, Wang, Hong, Song, Zhengbo, Yang, Nong, Zhang, Yongchang
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Sprache:eng
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Zusammenfassung:•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. 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. 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. 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). 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 chemo
ISSN:0169-5002
1872-8332
DOI:10.1016/j.lungcan.2021.03.006