Background: About 10% of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations are harbored as uncommon mutations. This study aimed to explore the efficacy and safety of dacomitinib, a second-generation EGFR tyrosine kinase inhibitor (EGFR-TKIs), in treating uncommon EGFR-mutated advanced NSCLC.
Methods: Treatment-naïve advanced NSCLC patients treated with dacomitinib at Hunan Cancer Hospital with uncommon EGFR mutations were evaluated. The primary endpoint was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety.
Result: Between December 2019 and December 2021, a total of 16 patients was included. Median PFS was 14.0 (95% CI 4.32-23.7) months, and median OS was not reached. ORR was 68.8% (95% CI 41.3 to 89.0%) and DCR was 93.8% (95%CI 69.8 to 99.8%), including three achieving complete remission (CR) and eight achieving partial remission (PR). Median PFS for patients with brain metastasis was 9.0 (95%CI 6.9 to 11.1) months. Intracranial ORR was 100%, including 2 CR and 4 PR. Major treatment-related adverse events (TRAEs) included rash (87.5%), paronychia (62.5%), oral ulcers (50.0%), and diarrhea (50.0%), none of which were ≥ grade 3 TRAEs.
Conclusions: Dacomitinib showed good activity and manageable toxicity in NSCLC patients with uncommon EGFR mutations.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577935 | PMC |
http://dx.doi.org/10.1186/s12885-023-11465-2 | DOI Listing |
Cell Rep Med
January 2025
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei New ΙΙ Han Institute for Integrative Lung Cancer Research, Yonsei University of Medicine, Seoul, Republic of Korea. Electronic address:
Uncommon epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) pose therapeutic challenge due to limited response to EGFR tyrosine kinase inhibitors (TKIs). This study presents preclinical evidence and mechanistic insights into the combination of lazertinib, a third-generation EGFR-TKI; and amivantamab, an EGFR-MET bispecific antibody, for treating NSCLC with uncommon EGFR mutations. The lazertinib-amivantamab combination demonstrates significant antitumor activity in patient-derived models with uncommon EGFR mutations either before treatment or after progressing on EGFR-TKIs.
View Article and Find Full Text PDFAnticancer Drugs
January 2025
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning.
Uncommon atypical mutations account for 10-15% of all epidermal growth factor receptor (EGFR) activating mutations in nonsmall-cell lung cancer (NSCLC). Tumors harboring rare EGFR mutations show highly heterogeneous responses to EGFR tyrosine kinase inhibitors (TKIs). There is insufficient clinical evidence for uncommon types of EGFR mutations, especially those with compound EGFR mutations.
View Article and Find Full Text PDFClin Lung Cancer
December 2024
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Medicine, Chicago, IL.
Background: Activating mutations in the epidermal growth factor receptor (EGFR) gene occur in 7% to 23% of patients with non-small-cell lung cancer (NSCLC). A small proportion of these (3-5%) are exon 18 mutations. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), had activity in the phase II SUMMIT basket study.
View Article and Find Full Text PDFObjectives: This study aimed to compare the overall survival (OS) of patients with advanced EGFR-mutant NSCLC treated with first-line osimertinib versus earlier-generation EGFR tyrosine kinase inhibitors (TKIs) in a real-world setting. Secondary endpoint included OS in patients with uncommon EGFR mutations. Exploratory aim focused on the impact of TKIs sequencing strategies.
View Article and Find Full Text PDFNeurol Neuroimmunol Neuroinflamm
March 2025
MeLis Institute, SynatAc Team, Inserm U1314/ UMR CNRS5284, France.
Background And Objectives: Breast cancers (BCs) of patients with paraneoplastic neurologic syndromes and anti-Yo antibodies (Yo-PNS) overexpress human epidermal growth factor receptor 2 (HER2) and display genetic alterations and overexpression of the Yo-onconeural antigens. They are infiltrated by an unusual proportion of B cells. We investigated whether these features were also observed in patients with PNS and anti-Ri antibodies (Ri-PNS).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!