Background: Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) capable of overcoming non-small cell lung cancer (NSCLC) with EGFR T790M mutation. Although the addition of bevacizumab to 1st generation EGFR-TKIs confers a significant improvement in progression-free survival (PFS) in treatment-naive EGFR mutant NSCLC patients, osimertinib plus bevacizumab combination failed to show prolongation in the phase 2 study WJOG8715L. Data of such combination in Chinese patients are still lacking. This study aimed to explore the efficacy of the addition of bevacizumab to osimertinib as second-line therapy in real-world data, and to evaluate the role of anti-angiogenesis plus osimertinib combination therapeutic strategies in pretreated Chinese NSCLC patients with acquired EGFR T790M mutation.
Methods: A total of 42 advanced NSCLC patients with acquired EGFR T790M mutation after prior EGFR-TKIs treatment were collected between January 2020 to August 2021, with 16 cases treated with osimertinib plus bevacizumab and 26 cases treated with osimertinib. The treatment effect of patients were analyzed.
Results: The objective response rate (ORR) in combination group and osimertinib group were 43.8% and 50.0% respectively (P=0.694). No statistically significant difference in median PFS (14.0 mon vs 13.0 mon, P=0.797) and overall survival (OS) (29.0 mon vs 26.0 mon, P=0.544) between the combination group and osimertinib group were observed. Prior history of bevacizumab was identified as an independent predictor of PFS (P=0.045) and OS (P=0.023).
Conclusions: Our study demonstrated that adding bevacizumab to osimertinib could not show advantages in PFS and OS in pretreated NSCLC patients harboring EGFR T790M-mutation.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2022.101.56 | DOI Listing |
Cancer Sci
December 2024
Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the standard therapy for patients harboring T790M after first-generation EGFR-TKI resistance. However, the impact of acquired EGFR amplification on the efficacy of third-generation EGFR-TKI against T790M remains uncertain. We aimed to investigate whether the presence of acquired EGFR amplification after first-generation EGFR-TKI resistance influences the efficacy of third-generation EGFR-TKI in patients with advanced non-small-cell lung cancer (NSCLC).
View Article and Find Full Text PDFJ Natl Compr Canc Netw
December 2024
1Division of Thoracic Tumor Multimodality Treatment, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
EGFR tyrosine kinase inhibitors (TKIs) have significantly improved clinical outcomes for patients with non-small cell lung cancer (NSCLC) harboring EGFR-activating mutations. However, resistance to TKI therapy often develops due to secondary EGFR mutations or the activation of bypass signalling pathways. Next-generation sequencing (NGS) can efficiently identify actionable genetic alterations throughout treatment.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2025
Department of Pharmaceutical Chemistry, Division of Computer-Aided Drug Design, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India.
A series of 2,4-disubstituted pyrimidine derivatives bearing 5-substituted-1,3,4 thidiazole were devised and synthesized based on the binding mode of the approved drug Osimertinib with the ATP competitive site of EGFR-L858R/T790M in order to increase selectivity towards double mutant EGFR and potent antitumor activity. Their cellular bioactivity and corresponding enzyme inhibition were studied, and it was revealed that several compounds had significant biological activity and selectivity when compared to the control compounds. One of the most promising compound 8, substantially suppressed the proliferation of H1975 cells and showed significant inhibition of double mutant EGFR-L858R/T790M TK with IC values of 0.
View Article and Find Full Text PDFClin Transl Med
January 2025
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Background: Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) remains a significant hurdle for patients with EGFR-mutated non-small cell lung cancer (NSCLC), particularly those lacking the EGFR. IMpower 150 study demonstrated promising efficacy for a combination of immune-chemotherapy and bevacizumab in patients with EGFR-mutated NSCLC.
Methods: This open-label, single-arm, phase II trial evaluated the efficacy and immune cell profile of the modified regimen combining atezolizumab, bevacizumab (7.
J Egypt Natl Canc Inst
December 2024
Department of Clinical Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
Background: Lung cancer is a form of cancer that is responsible for the largest incidence of deaths attributed to cancer worldwide. Non-small cell lung cancer (NSCLC) is the most prevalent of all the subtypes of the disease. Treatment with tyrosine kinase inhibitors (TKI) may help some people who have been diagnosed with non-small cell lung cancer.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!