PMID- 35770100 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 13 DP - 2022 TI - Dacomitinib for Advanced Non-small Cell Lung Cancer Patients Harboring Major Uncommon EGFR Alterations: A Dual-Center, Single-Arm, Ambispective Cohort Study in China. PG - 919652 LID - 10.3389/fphar.2022.919652 [doi] LID - 919652 AB - Objective: Dacomitinib has been approved for non-small-cell lung cancer (NSCLC) patients harboring classical epidermal growth factor receptor (EGFR) mutations; however, clinical evidence of its activity on major uncommon EGFR mutations is currently limited. Materials and methods: This was a dual-center, single-arm, ambispective cohort study in China. Patients with histologically confirmed metastatic or recurrent NSCLC harboring major uncommon EGFR mutations were eligible for the study. The objective response rate and disease control rate were determined by RECIST 1.1 every 1-2 months. Adverse events were assessed by CTCAE 5.0. Results: In total, 32 NSCLC patients were enrolled between July 2020 and January 2022, and 18 (56.3%) patients received dacomitinib as first-line therapy. Median age was 64 years, and 20 (62.5%) were female. The mutations identified were G719X (n = 24; 75%), followed by L861X (n = 10; 31.3%), and S768I (n = 8; 25%). In the first-line setting, 72.2% of patients (13/18) had a confirmed partial response and 100% (18/18) had disease control, and the median progression-free survival (PFS) and overall survival (OS) were unreached. In the whole cohort, 56.3% of patients (18/32) had a confirmed partial response and 90.6% (29/32) had disease control, and the median PFS was 10.3 months (95% confidence interval, 6.1-14.5) and the median OS was 36.5 months. Except for one case not available for brain re-evaluation, control of the intracranial metastases was observed in 13 patients (13/14, 92.9%). No grade 4-5 adverse events (AEs) occurred, but all patients had grade 1-2 AEs, and 12.5% (4/32) patients required a dosage reduction due to intolerable AEs. Conclusions: Dacomitinib demonstrated favorable activity with manageable toxicity in patients with NSCLC harboring major uncommon EGFR mutations. CI - Copyright (c) 2022 Li, Yang, Cai, Li, Xu, Zhang, Zhou, Wang, Wang, Hu, Yan and Wang. FAU - Li, Hong-Shuai AU - Li HS AD - Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Yang, Guang-Jian AU - Yang GJ AD - Department of Respiratory Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji'nan, China. FAU - Cai, Yi AU - Cai Y AD - Independent Researcher, Ellicott City, MD, United States. FAU - Li, Jun-Ling AU - Li JL AD - Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Xu, Hai-Yan AU - Xu HY AD - Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Zhang, Tao AU - Zhang T AD - Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Zhou, Li-Qiang AU - Zhou LQ AD - Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Wang, Yu-Ying AU - Wang YY AD - Department of Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China. FAU - Wang, Jin-Liang AU - Wang JL AD - Department of Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China. FAU - Hu, Xing-Sheng AU - Hu XS AD - Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Yan, Xiang AU - Yan X AD - Department of Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China. FAU - Wang, Yan AU - Wang Y AD - Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. LA - eng PT - Journal Article DEP - 20220613 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC9234690 OTO - NOTNLM OT - dacomitinib OT - efficacy OT - major uncommon EGFR mutations OT - non-small cell lung cancer OT - safety COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/07/01 06:00 MHDA- 2022/07/01 06:01 PMCR- 2022/06/13 CRDT- 2022/06/30 02:50 PHST- 2022/04/13 00:00 [received] PHST- 2022/05/18 00:00 [accepted] PHST- 2022/06/30 02:50 [entrez] PHST- 2022/07/01 06:00 [pubmed] PHST- 2022/07/01 06:01 [medline] PHST- 2022/06/13 00:00 [pmc-release] AID - 919652 [pii] AID - 10.3389/fphar.2022.919652 [doi] PST - epublish SO - Front Pharmacol. 2022 Jun 13;13:919652. doi: 10.3389/fphar.2022.919652. eCollection 2022.