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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Molecular correlation of response to pyrotinib in advanced NSCLC with HER2 mutation: biomarker analysis from two
Shiqi Mao1, Shuo Yang1, Xinyu Liu1
1Department of Medical Oncology, Shanghai Pulmonary Hospital, Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, China.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Trial Registration:
The patients were from two registered clinical trials (ClinicalTrials.gov: NCT02535507, NCT02834936).
Insights
Patients with TP53 wild type and non-shedding or cleared circulating tumor DNA (ctDNA) showed better response to pyrotinib treatment for HER2-mutated non-small cell lung cancer (NSCLC). These biomarkers may guide pyrotinib use in advanced NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- HER2-mutated non-small cell lung cancer (NSCLC) has limited treatment options with moderate efficacy from current therapies.
- Targeted therapies like antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) offer potential but require further optimization.
- Identifying predictive biomarkers is crucial for improving treatment outcomes in advanced NSCLC.
Purpose of the Study:
- To investigate the molecular features associated with response to pyrotinib in patients with advanced HER2-mutated NSCLC.
- To identify potential biomarkers that predict efficacy of pyrotinib treatment.
- To correlate circulating tumor DNA (ctDNA) profiles with treatment outcomes.
Main Methods:
- A pooled analysis of patients from two phase II clinical trials (NCT02535507, NCT02834936).
- Next-generation sequencing (NGS) panels were used to analyze baseline plasma ctDNA.
- Correlation between ctDNA features (nonshedding, clearance) and TP53 status with pyrotinib efficacy (ORR, PFS, OS) was investigated.
Main Results:
- The study included 50 patients with baseline plasma samples, showing an overall objective response rate (ORR) of 28% and median progression-free survival (PFS) of 7.0 months.
- Patients with TP53 wild type demonstrated significantly higher disease control rates, PFS, and overall survival (OS) compared to those with TP53 mutations.
- ctDNA nonshedding and clearance were associated with significantly longer PFS and a trend towards longer OS compared to non-clearance.
Conclusions:
- TP53 wild type status, ctDNA nonshedding, and ctDNA clearance are associated with superior pyrotinib efficacy in HER2-mutated advanced NSCLC.
- These molecular features may serve as predictive biomarkers to guide the clinical application of pyrotinib.
- Further research is warranted to validate these findings and optimize treatment strategies for NSCLC.
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