PMID- 30791921 OWN - NLM STAT- MEDLINE DCOM- 20200401 LR - 20200401 IS - 1479-5876 (Electronic) IS - 1479-5876 (Linking) VI - 17 IP - 1 DP - 2019 Feb 21 TI - Crizotinib with or without an EGFR-TKI in treating EGFR-mutant NSCLC patients with acquired MET amplification after failure of EGFR-TKI therapy: a multicenter retrospective study. PG - 52 LID - 10.1186/s12967-019-1803-9 [doi] LID - 52 AB - BACKGROUND: MET amplification is associated with acquired resistance to first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in treating non-small-cell lung cancer (NSCLC); however, the therapeutic strategy in these patients is undefined. Herein we report the clinical outcomes of patients with c-MET amplification resistance to EGFR-TKIs treated with crizotinib. METHODS: We retrospectively analyzed advanced NSCLC patients from five sites who were diagnosed with EGFR-mutant NSCLC and received EGFR-TKI treatment. After disease progression, these patients were confirmed to have a MET-to-centromere ratio (MET:CEN) >/= 1.8 based on fluorescence in situ hybridization (FISH) examination and without a T790M mutation. We assessed the efficacy and safety of crizotinib to overcome EGFR-TKI resistance in EGFR-activating mutations NSCLC with acquired MET amplification. RESULTS: Amplification of the acquired MET gene was identified in 18 patients with EGFR-mutant NSCLC. Fourteen patients received crizotinib treatment after acquired resistance to EGFR-TKIs. Among the 14 patients, 6 (42.9%) received crizotinib plus EGFR-TKI and 8 (57.1%) received crizotinib monotherapy. The overall objective response rate (ORR) and disease control rate (DCR) were 50.0% (7/14) and 85.7% (12/14), respectively. The median PFS (mPFS) of patients receiving crizotinib monotherapy and crizotinib plus EGFR-TKI was 6.0 and 12.6 months, respectively (P = 0.315). Notably, treatment efficacy was more pronounced in patients with crizotinib than patients with chemotherapy (24.0 months vs. 12.0 months, P = 0.046). The mOS for 8 of 14 patients receiving crizotinib monotherapy and 6 of 14 patients receiving crizotinib plus EGFR-TKI was 17.2 and 24.0 months, respectively (P = 0.862). Among the 14 patients, 1 who received crizotinib monotherapy (grade 3 nausea) and 2 who received crizotinib plus EGFR-TKI (grade 3 elevated liver aminotransferase levels) received reduced doses of crizotinib (200 mg twice daily) to better tolerate the dose. CONCLUSIONS: We observed the clinical evidence of efficacy generated by combination of crizotinib and previous EGFR-TKIs after the resistance to first-generation EGFR-TKIs. These results might increase evidence of more effective therapeutic strategies for NSCLC treatment. Combination therapy did not increase the frequency of adverse reactions. FAU - Wang, Wenxian AU - Wang W AUID- ORCID: 0000-0002-3047-4149 AD - Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, China. FAU - Wang, Hong AU - Wang H AD - Department of Lung Cancer, The Fifth Medical Center, General of PLA, Beijing, 100071, China. FAU - Lu, Peihua AU - Lu P AD - Department of Oncology, Wuxi People Hospital, Wuxi, 214023, China. FAU - Yu, Zongyang AU - Yu Z AD - Department of Oncology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, 350025, China. FAU - Xu, Chunwei AU - Xu C AD - Department of Pathology, Fujian Cancer Hospital, Fuzhou, 362200, China. FAU - Zhuang, Wu AU - Zhuang W AD - Department of Pathology, Fujian Cancer Hospital, Fuzhou, 362200, China. FAU - Song, Zhengbo AU - Song Z AD - Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, China. zheng_bo_song@163.com. AD - Department of Chemotherapy, Zhejiang Cancer Hospital, East Banshan Road, Hangzhou, 310022, China. zheng_bo_song@163.com. LA - eng GR - 2019RC027/Medical Scientific Research Foundation of Zhejiang Province/International PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20190221 PL - England TA - J Transl Med JT - Journal of translational medicine JID - 101190741 RN - 0 (Protein Kinase Inhibitors) RN - 53AH36668S (Crizotinib) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) SB - IM MH - Carcinoma, Non-Small-Cell Lung/diagnostic imaging/*drug therapy/genetics MH - Crizotinib/adverse effects/pharmacology/*therapeutic use MH - Disease Progression MH - Disease-Free Survival MH - ErbB Receptors/*genetics MH - Female MH - *Gene Amplification MH - Humans MH - Lung Neoplasms/diagnostic imaging/*drug therapy/genetics MH - Male MH - Middle Aged MH - Mutation/*genetics MH - Protein Kinase Inhibitors/adverse effects/*therapeutic use MH - Proto-Oncogene Proteins c-met/*genetics/metabolism MH - Retrospective Studies MH - Tomography, X-Ray Computed MH - Treatment Failure PMC - PMC6385446 OTO - NOTNLM OT - Crizotinib OT - EGFR OT - Lung cancer OT - MET amplification OT - Resistance OT - Survival EDAT- 2019/02/23 06:00 MHDA- 2020/04/02 06:00 PMCR- 2019/02/21 CRDT- 2019/02/23 06:00 PHST- 2018/12/04 00:00 [received] PHST- 2019/02/17 00:00 [accepted] PHST- 2019/02/23 06:00 [entrez] PHST- 2019/02/23 06:00 [pubmed] PHST- 2020/04/02 06:00 [medline] PHST- 2019/02/21 00:00 [pmc-release] AID - 10.1186/s12967-019-1803-9 [pii] AID - 1803 [pii] AID - 10.1186/s12967-019-1803-9 [doi] PST - epublish SO - J Transl Med. 2019 Feb 21;17(1):52. doi: 10.1186/s12967-019-1803-9.