PMID- 36358728 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221117 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 14 IP - 21 DP - 2022 Oct 28 TI - Afatinib and Dacomitinib Efficacy, Safety, Progression Patterns, and Resistance Mechanisms in Patients with Non-Small Cell Lung Cancer Carrying Uncommon EGFR Mutations: A Comparative Cohort Study in China (AFANDA Study). LID - 10.3390/cancers14215307 [doi] LID - 5307 AB - (1) Background: Afatinib has been approved for patients with non-small cell lung cancer (NSCLC) carrying major uncommon epidermal growth factor receptor gene (EGFR) mutations. Dacomitinib, another second-generation tyrosine kinase inhibitor, has also shown promising potential for uncommon EGFR mutations. However, no comparative study has been conducted. (2) Methods: Two cohorts were employed: the AFANDA cohort, an ambispective cohort including 121 patients with uncommon EGFR mutations admitted to two tertiary hospitals in China, and an external validation afatinib cohort (ex-AC), extracted from the Afatinib Uncommon EGFR Mutations Database (N = 1140). The AFANDA cohort was divided into an afatinib cohort (AC) and a dacomitinib cohort (DC) for internal exploration. Objective response rate (ORR), progression-free survival (PFS), and adverse events (AEs) were assessed for comparison. Progression patterns and resistance mechanisms were explored. (3) Results: In total, 286 patients with advanced NSCLC carrying uncommon EGFR mutations treated with afatinib or dacomitinib were enrolled, including 79 in the AFANDA cohort (44 in the DC, 35 in the AC) and 207 in the ex-AC. In internal exploration, the ORR of the DC was significantly higher than that of the AC (60.5 vs. 26.7%, p = 0.008), but there was no significant difference in median PFS between the DC and the AC (12.0 months vs. 10.0 months, p = 0.305). Multivariate analysis confirmed an independent favorable effect of dacomitinib on PFS (hazard ratio (HR), 1.909; p = 0.047). In external validation, multivariate analysis confirmed the independent prognostic role of dacomitinib in PFS (HR, 1.953; p = 0.029). Propensity score matching analysis confirmed the superiority of dacomitinib over afatinib in terms of PFS in both univariate and multivariate analyses. Toxicity profiling analysis suggested more G1 (p = 0.006), but fewer G3 (p = 0.036) AEs in the DC than in the AC. Progression patterns revealed that the incidence of intracranial progression in the AC was significantly higher than that in the DC (50 vs. 21.1%, p = 0.002). Drug resistance analysis indicated no significant difference in the occurrence of T790M between the AC and the DC (11.8 vs. 15.4%, p = 0.772). (4) Conclusions: Compared with afatinib, dacomitinib demonstrated a more favorable activity with manageable toxicity and different progression patterns in patients with NSCLC carrying uncommon EGFR mutations. 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 100021, China. FAU - Wang, Shou-Zheng AU - Wang SZ AUID- ORCID: 0000-0003-3697-4643 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 100021, China. AD - Department of Medical Oncology, Beijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Research Institute, Capital Medical University, Beijing 101149, China. FAU - Xu, Hai-Yan AU - Xu HY AD - Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Yan, Xiang AU - Yan X AUID- ORCID: 0000-0002-3683-474X AD - Department of Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing 100000, China. FAU - Zhang, Jin-Yao AU - Zhang JY 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 100021, China. FAU - Lei, Si-Yu AU - Lei SY AUID- ORCID: 0000-0001-6325-660X 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 100021, China. FAU - Li, Teng AU - Li 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 100021, China. FAU - Hao, Xue-Zhi AU - Hao XZ 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 100021, China. FAU - Zhang, Tao AU - Zhang T AD - Department of Radiotherapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100000, 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 250000, 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 100021, China. FAU - Liu, Peng AU - Liu P 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 100021, China. FAU - Wang, Yu-Ying AU - Wang YY AD - Department of Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing 100000, 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 100021, China. FAU - Xing, Pu-Yuan AU - Xing PY 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 100021, China. FAU - Wang, Yan AU - Wang Y AUID- ORCID: 0000-0002-1743-6383 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 100021, China. LA - eng GR - (Grant No. 2021-053-ZZ)./Beijing Health Promotion Association/ PT - Journal Article DEP - 20221028 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC9656097 OTO - NOTNLM OT - afatinib OT - dacomitinib OT - efficacy OT - non-small cell lung cancer OT - progression patterns OT - resistance OT - safety OT - uncommon EGFR mutations COIS- The authors declare no conflict of interest. EDAT- 2022/11/12 06:00 MHDA- 2022/11/12 06:01 PMCR- 2022/10/28 CRDT- 2022/11/11 01:06 PHST- 2022/09/28 00:00 [received] PHST- 2022/10/19 00:00 [revised] PHST- 2022/10/26 00:00 [accepted] PHST- 2022/11/11 01:06 [entrez] PHST- 2022/11/12 06:00 [pubmed] PHST- 2022/11/12 06:01 [medline] PHST- 2022/10/28 00:00 [pmc-release] AID - cancers14215307 [pii] AID - cancers-14-05307 [pii] AID - 10.3390/cancers14215307 [doi] PST - epublish SO - Cancers (Basel). 2022 Oct 28;14(21):5307. doi: 10.3390/cancers14215307.