Objectives: Epidermal growth factor receptor (EGFR) exon 20 insertions comprise 4-10 % of EGFR mutations in non-small cell lung cancer (NSCLC) and are associated with primary resistance to first and second generation EGFR tyrosine kinase inhibitors (TKIs). In vitro and preclinical animal studies have shown that osimertinib exerts antitumor activity against EGFR exon 20 mutation positive NSCLC. We report on a cohort of advanced stage NSCLC patients who harbor an EGFR exon 20 mutation and received osimertinib treatment.
Material And Methods: Twenty-one patients were treated with osimertinib 80 or 160 mg once daily from April 2016 to June 2018, in four institutions in the Netherlands. Data were obtained retrospectively. Progression free survival (PFS), disease control rate (DCR), overall survival (OS) and objective response rate (ORR) were assessed using RECIST v1.1.
Results: Thirteen patients received prior platinum-based chemotherapy, and three patients a first - or second generation EGFR TKI. We observed 1 partial response, 17 patients with stable disease and 3 with progressive disease as best response to osimertinib (ORR 5 %). Median PFS was 3.6 (95 % CI, 2.6-4.5) months. PFS did not differ for patients with co-occurring TP53 mutations (p = 0.937). The DCR at three months was 71 %. Median OS was 8.7 (95 % CI, 1.1-16.4) months.
Conclusion: Osimertinib has limited antitumor activity in patients with EGFR exon 20 mutated NSCLC, with an ORR of 5 %.
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http://dx.doi.org/10.1016/j.lungcan.2019.12.013 | DOI Listing |
Ecancermedicalscience
November 2024
Instituto Venezolano de Investigaciones Científicas (IVIC), Unidad de Estudios Genéticos y Forenses (UEGF), Caracas 1020, República Bolivariana de Venezuela.
Colorectal cancer (CRC) is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women. The epidermal growth factor receptor (EGFR) is relevant in the development and progression of CRC, because it is part of multiple signaling pathways involved in processes of the cell cycle, their malfunction causes dysregulation and subsequently carcinogenesis. Consequently, therapies were developed with anti-EGFR monoclonal antibodies (MAbs) that improve the survival of patients with CRC.
View Article and Find Full Text PDFClin Pharmacol Drug Dev
January 2025
Takeda Development Center Americas, Inc., Cambridge, MA, USA.
Mobocertinib is a kinase inhibitor designed to selectively target epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations in non-small cell lung cancer. This drug-drug interaction study assessed the effect of multiple-dose administration of mobocertinib on the pharmacokinetics (PK) of midazolam, a sensitive cytochrome P450 3A substrate. Patients with locally advanced or metastatic non-small cell lung cancer refractory/intolerant to standard available therapy were enrolled.
View Article and Find Full Text PDFAnn Surg Oncol
January 2025
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Background: Tumor microvasculature is an important component of the tumor microenvironment (TME), and it has been reported that tumor microvasculature induces TME to become immunosuppressive via vascular endothelial growth factor. However, the significance of this in adenocarcinoma with epidermal growth factor receptor (EGFR) common mutations has not been fully investigated.
Methods: We analyzed 262 patients with adenocarcinoma harboring EGFR common mutations who underwent surgery at Kyushu University Hospital between 2006 and 2021.
Nephrol Dial Transplant
January 2025
Department of Nephrology, Kidney Transplantation and Dialysis, CHU Lille, University of Lille, Lille, France.
Background And Hypothesis: Unlike X-linked or autosomal recessive Alport Syndrome, no clear genotype/phenotype correlation has yet been demonstrated in patients carrying a single variant of COL4A3 or COL4A4.
Methods: We carried out a multicenter retrospective study to assess the risk factors involved in renal survival in patients presenting a single pathogenic variant on COL4A3 or COL4A4.
Results: 97 patients presenting a single pathogenic variant of COL4A3 or COL4A4 were included.
Front Med
January 2025
Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
SMARCA4-deficient non small cell lung cancer (SMARCA4-dNSCLC) has recently garnered increasing attention due to its high malignancy and poor prognosis. The literature suggests that in non small cell lung cancer (NSCLC), the loss of SMARCA4 frequently co-occurs with mutations in KRAS, KEAP1, and STK11 rather than in EGFR, ALK, and ROS1. Herein, we present the first documented case of SMARCA4-dNSCLC accompanied with rare mutations of EGFR exon 20 S768I and exon 18 G719X.
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