Haiyan Yang1, Zhen Zhou2, Li Lin3, Mingxia Yang4, Chong Li5, Ziming Li2, Xinmin Yu6, Analyn Lizaso7, Han Han-Zhang7, Bing Li7, Jianxing Xiang7, Xinru Mao7, Qinqin Xu8, Yongchang Zhang9, Nong Yang10. 1. 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, China. 2. Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China. 3. Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China; Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin, China. 4. Changzhou Second People's Hospital Nanjing Medical University, Changzhou, Jiangsu, China. 5. Department of Respiration, The First People's Hospital of Changzhou, Changzhou, Jiangsu, China. 6. Department of Thoracic Oncology, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China. 7. Burning Rock Biotech, Guangzhou, China. 8. Department of Medical Oncology, Qinghai Provincial People's Hospital, Xining, China. 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, China. Electronic address: zhangyongchang@csu.edu.cn. 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, China. Electronic address: yangnong0217@163.cn.
Abstract
BACKGROUND: Most studies on MET exon 14 (MET-ex14) alteration, defined as an oncogenic driver, have been carried out among Caucasians; similar studies among Chinese people are limited. METHODS: We retrospectively analyzed the genomic profiles of 11,306 Chinese patients with various stages of lung cancer to investigate the prevalence of MET-ex14. Survival outcomes were analyzed in evaluable patients who received front-line crizotinib (n = 44) or chemotherapy (n = 14). RESULTS: MET-ex14 alterations were identified in 125 patients, a frequency of 1.1 %, which is much lower than that in Caucasians (∼2.7 %). We found that MET-ex14 alterations were more likely to be detected in older patients (median age 69.0 years, p <0.001). Among evaluable patients harboring MET-ex14 alterations, longer progression-free survival (PFS) was observed with crizotinib than with chemotherapy (8.5 months versus 4.0 months, p = 0.041), but there was no difference in overall survival (OS, 11.3 months versus 12.0 months, p = 0.66). No significant difference in PFS or OS was found among MET splice-site variants or when there were concurrent TP53 alterations. Concurrent MET amplification results in a shorter PFS (4.2 months versus 8.5 months, p = 0.029) but a comparable OS (7.8 months versus 14.0 months, p = 0.12). Patients with undetectable baseline plasma MET-ex14 had a trend of longer PFS (p = 0.097) but comparable OS (p = 0.18). A novel MET Y1003C mutation was detected and demonstrated a clinical response to crizotinib. CONCLUSIONS: Our study demonstrated a prevalence of 1.1 % for MET-ex14 alterations among the Chinese population. Our study also contributes to a better understanding of molecular factors that are associated with clinical outcomes of patients with MET exon 14 alterations.
BACKGROUND: Most studies on MET exon 14 (MET-ex14) alteration, defined as an oncogenic driver, have been carried out among Caucasians; similar studies among Chinese people are limited. METHODS: We retrospectively analyzed the genomic profiles of 11,306 Chinese patients with various stages of lung cancer to investigate the prevalence of MET-ex14. Survival outcomes were analyzed in evaluable patients who received front-line crizotinib (n = 44) or chemotherapy (n = 14). RESULTS:MET-ex14 alterations were identified in 125 patients, a frequency of 1.1 %, which is much lower than that in Caucasians (∼2.7 %). We found that MET-ex14 alterations were more likely to be detected in older patients (median age 69.0 years, p <0.001). Among evaluable patients harboring MET-ex14 alterations, longer progression-free survival (PFS) was observed with crizotinib than with chemotherapy (8.5 months versus 4.0 months, p = 0.041), but there was no difference in overall survival (OS, 11.3 months versus 12.0 months, p = 0.66). No significant difference in PFS or OS was found among MET splice-site variants or when there were concurrent TP53 alterations. Concurrent MET amplification results in a shorter PFS (4.2 months versus 8.5 months, p = 0.029) but a comparable OS (7.8 months versus 14.0 months, p = 0.12). Patients with undetectable baseline plasma MET-ex14 had a trend of longer PFS (p = 0.097) but comparable OS (p = 0.18). A novel METY1003C mutation was detected and demonstrated a clinical response to crizotinib. CONCLUSIONS: Our study demonstrated a prevalence of 1.1 % for MET-ex14 alterations among the Chinese population. Our study also contributes to a better understanding of molecular factors that are associated with clinical outcomes of patients with MET exon 14 alterations.
Authors: Xiuning Le; Lingzhi Hong; Chuck Hensel; Rongrong Chen; Haley Kemp; Niamh Coleman; Christine A Ciunci; Stephen V Liu; Marcelo V Negrao; Jennifer Yen; Xuefeng Xia; Juergen Scheuenpflug; Christopher Stroh; Dilafruz Juraeva; Anne Tsao; David Hong; Victoria Raymond; Paul Paik; Jianjun Zhang; John V Heymach Journal: JCO Precis Oncol Date: 2021-12-13