Wenxian Wang1, Chunwei Xu2, Huafei Chen3, Jinhao Jia4, Liping Wang5, Huijing Feng6, Hong Wang7, Zhengbo Song8, Nong Yang9, Yongchang Zhang10. 1. Department of Medical Oncology, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, 310022, China; Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China. 2. Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210002, China. 3. Department of Thoracic Disease Center, Zhejiang Rongjun Hospital, Jiaxing, Zhejiang, 314000, China. 4. Department of Chemoradiotherapy, Tangshan People's Hospital, Tangshan, Hebei, 063001, China. 5. Department of Oncology, Baotou Cancer Hospital, Baotou, Inner Mongolia, 014000, China. 6. Department of Thoracic Oncology, Shanxi Academy of Medical Sciences, Shanxi Bethune Hospital, Taiyuan, Shanxi, 030032, China. 7. Department of Lung Cancer, The Fifth Medical Center, General Hospital of PLA, Beijing, 100071, China. 8. Department of Medical Oncology, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, 310022, China; Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China. Electronic address: zheng_bo_song@163.com. 9. Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, China. Electronic address: yangnong0217@163.com. 10. Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, China. Electronic address: zhangyongchang@csu.edu.cn.
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.
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.