{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Mao S"],"funding":["Science and Technology Commission of Shanghai Municipality","Shanghai Innovative Collaboration Project","Shanghai Shenkang Hospital Development Center","National Natural Science Foundation of China","Clinical Research foundation of Shanghai Pulmonary Hospital"],"pagination":["53"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10251549"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(1)"],"pubmed_abstract":["<h4>Background</h4>Non-small cell lung cancer (NSCLC) with HER2 mutation has entered into the era of targeted therapy. However, both anti-HER2 antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) showed moderate objective response rate (ORR) and median progression-free survival (PFS). The aim of this study was to investigate the molecular features of responders to pyrotinib in advanced NSCLC with HER2 mutation.<h4>Methods</h4>Patients from our two previous phase II trials were pooled analyzed. Their circulating tumor DNA (ctDNA) were detected by next-generation sequencing (NGS) panels, and the correlation with the efficacy of pyrotinib was investigated.<h4>Results</h4>This pooled analysis included 75 patients, and 50 of them with baseline plasma samples were finally enrolled with a median age of 57 years old. The overall ORR and median PFS were 28% and 7.0 months respectively. Biomarker analysis showed that 5 patients were ctDNA nonshedding. Patients with TP53 wild type were significantly associated with higher disease control rate (97.1%vs. 68.8%, p = 0.010), PFS (median 8.4 vs. 2.8 months, p = 0.001) and overall survival (OS, median 26.7 vs. 10.4 months, p < 0.001) than those with mutations. ctDNA of nonshedding and clearance exhibited significantly longer PFS (median: 10.2 vs. 9.8 vs. 5.6 months, p = 0.036) and a trend of longer OS (median: 35.3 vs. 18.1 vs. 14.6 months, p = 0.357) than those not.<h4>Conclusion</h4>Patients with TP53 wild type, ctDNA nonshedding, or clearance showed superior efficacy of pyrotinib in patients with HER2-mutated advanced NSCLC, which might be helpful to guide the utility of pyrotinib in clinical setting.<h4>Trial registration</h4>The patients were from two registered clinical trials (ClinicalTrials.gov: NCT02535507, NCT02834936)."],"journal":["Experimental hematology & oncology"],"pubmed_title":["Molecular correlation of response to pyrotinib in advanced NSCLC with HER2 mutation: biomarker analysis from two phase II trials."],"pmcid":["PMC10251549"],"funding_grant_id":["No.82002419","No. FKLY20008","No. 2020CXJQ02","No. 81972167","No. 21XD1423200","No. SHDC12019133"],"pubmed_authors":["Mao S","Chen J","Zhang J","Lin X","Gao G","Jiang T","Wu F","Liu X","Li X","Yang Y","Wang Q","Zhang Y","Zhou C","Zhu X","Wang Y","Yang S","Ren S"],"additional_accession":[]},"is_claimable":false,"name":"Molecular correlation of response to pyrotinib in advanced NSCLC with HER2 mutation: biomarker analysis from two phase II trials.","description":"<h4>Background</h4>Non-small cell lung cancer (NSCLC) with HER2 mutation has entered into the era of targeted therapy. However, both anti-HER2 antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) showed moderate objective response rate (ORR) and median progression-free survival (PFS). The aim of this study was to investigate the molecular features of responders to pyrotinib in advanced NSCLC with HER2 mutation.<h4>Methods</h4>Patients from our two previous phase II trials were pooled analyzed. Their circulating tumor DNA (ctDNA) were detected by next-generation sequencing (NGS) panels, and the correlation with the efficacy of pyrotinib was investigated.<h4>Results</h4>This pooled analysis included 75 patients, and 50 of them with baseline plasma samples were finally enrolled with a median age of 57 years old. The overall ORR and median PFS were 28% and 7.0 months respectively. Biomarker analysis showed that 5 patients were ctDNA nonshedding. Patients with TP53 wild type were significantly associated with higher disease control rate (97.1%vs. 68.8%, p = 0.010), PFS (median 8.4 vs. 2.8 months, p = 0.001) and overall survival (OS, median 26.7 vs. 10.4 months, p < 0.001) than those with mutations. ctDNA of nonshedding and clearance exhibited significantly longer PFS (median: 10.2 vs. 9.8 vs. 5.6 months, p = 0.036) and a trend of longer OS (median: 35.3 vs. 18.1 vs. 14.6 months, p = 0.357) than those not.<h4>Conclusion</h4>Patients with TP53 wild type, ctDNA nonshedding, or clearance showed superior efficacy of pyrotinib in patients with HER2-mutated advanced NSCLC, which might be helpful to guide the utility of pyrotinib in clinical setting.<h4>Trial registration</h4>The patients were from two registered clinical trials (ClinicalTrials.gov: NCT02535507, NCT02834936).","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jun","modification":"2024-11-21T01:59:13.11Z","creation":"2024-11-21T01:59:13.11Z"},"accession":"S-EPMC10251549","cross_references":{"pubmed":["37296463"],"doi":["10.1186/s40164-023-00417-y"]}}