PMID- 37604026 OWN - NLM STAT- MEDLINE DCOM- 20230919 LR - 20230926 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 184 DP - 2023 Oct TI - Efficacy and safety of re-challenging 160 mg furmonertinib for advanced NSCLC after resistance to third-generation EGFR-TKIs targeted agents: A real-world study. PG - 107346 LID - S0169-5002(23)00884-X [pii] LID - 10.1016/j.lungcan.2023.107346 [doi] AB - BACKGROUND: Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) show good selectivity for classical EGFR mutated and EGFR T790M mutated non-small cell lung cancer (NSCLC). However, resistance inevitably occurs to third-generation EGFR-TKI. This study describes the real-world characteristics, efficacy, and safety of treating post-progression NSCLC with 160 mg of furmonertinib (in combination with or without anti-angiogenic agents and chemotherapy) with third-generation EGFR-TKIs. METHODS: EGFR-mutated NSCLC patients with intracranial progression pattern cohort (IP cohort) or extracranial progression pattern cohort (EP cohort) were retrospectively analyzed following progression to third-generation EGFR-TKIs receiving furmonertinib 160 mg daily as second-line or later treatment in combination with or without anti-angiogenic agents and chemotherapy. RESULTS: Thirty-nine patients were included and categorized into two groups according to the progression pattern. Then, 22 patients in the IP cohort and 17 patients in the EP cohort, most of whom were in poor physical condition, were included and 84.6% had central nervous system metastases. In the IP cohort, the median PFS was 5.5 months (95% CI 4.67-8.72), and the median OS was 9.8 months (95% CI 7.25-11.20) for single-agent furmonertinib or combination therapy. In the EP cohort, the median PFS was 3.2 months (95% CI 2.18-4.70), and the median OS was 6.7 months (95% CI 4.99-8.75). Univariate analysis showed the association between the presence of a prior T790M mutation and a history of combined radiotherapy with longer PFS with furmonertinib (p = 0.048, p = 0.004). Overall, adverse events (AEs) of any grade occurred in 84.6% of patients (33/39), with the majority having grade 2 or lower AEs. CONCLUSION: Furmonertinib 160 mg is an optional regimen for patients with advanced NSCLC who develop resistance after treatment with third-generation EGFR-TKIs, especially those developing resistance due to the progression of intracranial lesions, with good efficacy and an acceptable safety profile that warrants further exploration. CI - Copyright (c) 2023 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Qi, Rongbin AU - Qi R AD - Department of Respiratory Medicine, TaiZhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, China. FAU - Fu, Xinyu AU - Fu X AD - Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, Zhejiang, China. FAU - Yu, Yingying AU - Yu Y AD - Department of Respiratory Medicine, TaiZhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, China. FAU - Xu, Hailing AU - Xu H AD - Department of Respiratory Medicine, TaiZhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, China. FAU - Shen, Mo AU - Shen M AD - Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China. FAU - He, Susu AU - He S AD - Department of Respiratory Medicine, TaiZhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, China. Electronic address: hess1555@enzemed.com. FAU - Lv, Dongqing AU - Lv D AD - Department of Respiratory Medicine, TaiZhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, China. Electronic address: Lvdq@enzemed.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230817 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - A49A7A5YN4 (aflutinib) RN - EC 2.7.10.1 (ErbB Receptors) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Angiogenesis Inhibitors) RN - EC 2.7.10.1 (EGFR protein, human) SB - IM MH - Humans MH - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics MH - ErbB Receptors/genetics MH - *Lung Neoplasms/drug therapy/genetics MH - Mutation/genetics MH - Protein Kinase Inhibitors/therapeutic use MH - Retrospective Studies MH - Angiogenesis Inhibitors OTO - NOTNLM OT - EGFR-TKI OT - Furmonertinib OT - NSCLC OT - Re-challenging COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/08/22 00:42 MHDA- 2023/09/19 06:42 CRDT- 2023/08/21 18:05 PHST- 2023/07/11 00:00 [received] PHST- 2023/08/11 00:00 [revised] PHST- 2023/08/14 00:00 [accepted] PHST- 2023/09/19 06:42 [medline] PHST- 2023/08/22 00:42 [pubmed] PHST- 2023/08/21 18:05 [entrez] AID - S0169-5002(23)00884-X [pii] AID - 10.1016/j.lungcan.2023.107346 [doi] PST - ppublish SO - Lung Cancer. 2023 Oct;184:107346. doi: 10.1016/j.lungcan.2023.107346. Epub 2023 Aug 17.