PMID- 31208370 OWN - NLM STAT- MEDLINE DCOM- 20191211 LR - 20220603 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 19 IP - 1 DP - 2019 Jun 17 TI - EGFR exon 20 insertion mutations and response to osimertinib in non-small-cell lung cancer. PG - 595 LID - 10.1186/s12885-019-5820-0 [doi] LID - 595 AB - BACKGROUND: Epidermal growth factor receptor exon 20 insertion (EGFRex20ins) mutations represent approximately 4-12% of EGFR mutations and are generally refractory to the 1st and 2nd generation EGFR tyrosine kinase inhibitors (TKIs). Development of effective therapies for patients with EGFRex20ins mutant non-small-cell lung carcinoma (NSCLC) represents a great unmet need. Preclinical models have shown that osimertinib is active in NSCLC harboring EGFRex20ins, while the antitumor activity of osimertinib remains to be evaluated in patients with EGFRex20ins mutations. METHODS: Tumor genotyping was performed in 2316 Chinese NSCLC cases with targeted next generation sequencing (NGS) covering the whole exons of EGFR gene. The frequency and genetic characteristics of EGFRexon20ins mutations were analyzed. Furthermore, six patients with specific EGFRexon20ins mutations and receiving osimertinib 80 mg once daily were retrospectively included to assess the antitumor activity and safety of monotherapy osimertinib. RESULTS: EGFRex20ins mutations were identified in 4.8% (53/1095) of EGFR mutant NSCLC and 2.3% (53/2316) of all NSCLC cases. The most frequently identified EGFRexon20ins is A767_V769dup (17/53,32.1%). We found that the genetic characteristics of EGFRex20ins mutations in Chinese patients with NSCLC were comparable to those reported in Caucasian patients. Four patients with osimertinib therapy achieved partial response and the rest stable disease. Median progression free survival (PFS) was 6.2 months (95% confidence interval 5.0-12.9 months; range 4.9-14.6 months). The most common adverse events (AEs) were diarrhea (2/6), pruritis (2/6), stomatitis (1/6) and nausea (1/6). No grade 3 or more AEs were documented. CONCLUSIONS: This study revealed that the genetic characteristics of EGFRex20ins mutations in Chinese patients with NSCLC were comparable to those reported in Caucasian patients. Furthermore, our study firstly demonstrated promising antitumor activity of osimertinib in certain EGFRex20ins mutant advanced NSCLC patients, indicating that osimertinib treatment for EGFRex20ins positive patients deserves further study. FAU - Fang, Wenfeng AU - Fang W AD - Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. fangwf@sysucc.org.cn. FAU - Huang, Yihua AU - Huang Y AD - Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Hong, Shaodong AU - Hong S AD - Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Zhang, Zhonghan AU - Zhang Z AD - Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Wang, Minghui AU - Wang M AD - Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510220, People's Republic of China. FAU - Gan, Jiadi AU - Gan J AD - Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Wang, Wenjing AU - Wang W AD - OrigiMed, Inc, NO.115 XinJunhuan Road, Shanghai, 201114, People's Republic of China. FAU - Guo, Honglin AU - Guo H AD - OrigiMed, Inc, NO.115 XinJunhuan Road, Shanghai, 201114, People's Republic of China. FAU - Wang, Kai AU - Wang K AD - OrigiMed, Inc, NO.115 XinJunhuan Road, Shanghai, 201114, People's Republic of China. FAU - Zhang, Li AU - Zhang L AD - Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. zhangli@sysucc.org.cn. LA - eng GR - 2016YFC0905500/National Key R&D Program of China/ GR - 2016YFC0905503/National Key R&D Program of China/ GR - 81772476/National Natural Science Foundation of China/ GR - 81872499/National Natural Science Foundation of China/ GR - 81702283/National Natural Science Foundation of China/ GR - 81602005/National Natural Science Foundation of China/ GR - 2017B020227001/Science and Technology Program of Guangdong/ PT - Journal Article DEP - 20190617 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Acrylamides) RN - 0 (Aniline Compounds) RN - 0 (Antineoplastic Agents) RN - 3C06JJ0Z2O (osimertinib) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Acrylamides/administration & dosage/adverse effects/*therapeutic use MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Aniline Compounds/administration & dosage/adverse effects/*therapeutic use MH - Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics MH - Child MH - China MH - ErbB Receptors/genetics MH - Exons/*genetics MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy/genetics MH - Male MH - Middle Aged MH - *Mutagenesis, Insertional MH - Mutation Rate MH - Retrospective Studies MH - Treatment Outcome MH - Young Adult PMC - PMC6580637 OTO - NOTNLM OT - EGFRex20ins OT - NGS OT - NSCLC OT - Osimertinib COIS- The authors declare that they have no competing interests. EDAT- 2019/06/19 06:00 MHDA- 2019/12/18 06:00 PMCR- 2019/06/17 CRDT- 2019/06/19 06:00 PHST- 2019/01/24 00:00 [received] PHST- 2019/06/11 00:00 [accepted] PHST- 2019/06/19 06:00 [entrez] PHST- 2019/06/19 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2019/06/17 00:00 [pmc-release] AID - 10.1186/s12885-019-5820-0 [pii] AID - 5820 [pii] AID - 10.1186/s12885-019-5820-0 [doi] PST - epublish SO - BMC Cancer. 2019 Jun 17;19(1):595. doi: 10.1186/s12885-019-5820-0.