Related Experiment Video
Updated: Jun 20, 2026
Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Real-World Patient Characteristics, Mutational Landscape, and Outcomes in Advanced/Metastatic HER2-Mutant Non-Small
Christine M Lovly1, Christina Baik2, Misako Nagasaka3
1Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA.
Purpose:
This observational study assessed the real-world characteristics, treatments, and outcomes of US patients with HER2-mutant advanced non-small cell lung cancer (NSCLC) overall and according to HER2 mutation type (tyrosine kinase domain [TKD] and non-TKD).
Methods:
Deidentified data were extracted for patients with advanced/metastatic NSCLC from the Flatiron Health-Foundation Medicine NSCLC Clinico-Genomic Database. Patients with oncogenic HER2 mutations were included. The primary objectives were to assess the prevalence of HER2 mutations and coaberrations, treatment patterns, and real-world overall survival (OS).
Results:
Overall, 559/14,768 (3.8%) patients had HER2 mutations; 262 (1.8%) were oncogenic. Patients with oncogenic TKD mutations (n = 197) were more frequently younger, female, and never-smokers than those with oncogenic non-TKD mutations (n = 65) and had fewer oncogenic coaberrations. Among patients with oncogenic HER2 mutations who underwent first-line treatment (n = 193), most received platinum-based chemoimmunotherapy (30.5%) or chemotherapy alone (27.9%); 119 patients (61.7%) received second-line treatment. Median OS after first and second lines of treatment was 13.5 months (95% CI, 11.6 to 16.9) and 11.1 months (95% CI, 9.2 to 13.6), respectively. Median OS with first-line platinum-based chemoimmunotherapy was 21.1 (95% CI, 12.2 to NA) and 11.7 months (95% CI, 8.3 to NA) in patients with TKD/non-TKD mutations, respectively, and median OS with platinum-based chemotherapy alone was 9.1 (95% CI, 5.7 to 16.0) and 17.3 (95% CI, 13.6 to NA) months, respectively.
Conclusion:
NSCLC patients with oncogenic TKD HER2 mutations had different characteristics and genetic features than patients with non-TKD mutations. Real-world outcomes with first- and second-line standard-of-care treatment were suboptimal, highlighting the need for new treatment options for patients with advanced HER2-mutant NSCLC.
Insights
This study reveals that patients with HER2-mutant non-small cell lung cancer (NSCLC) with tyrosine kinase domain (TKD) mutations differ genetically from those with non-TKD mutations. Current treatments offer suboptimal outcomes, indicating a need for novel therapies for advanced NSCLC.
Area of Science:
- Oncology
- Genetics
- Clinical Research
Background:
- HER2 mutations are a rare but actionable subset of non-small cell lung cancer (NSCLC).
- Understanding the real-world characteristics and treatment patterns of HER2-mutant NSCLC is crucial for improving patient outcomes.
Purpose of the Study:
- To evaluate the real-world characteristics, treatments, and overall survival (OS) of US patients with HER2-mutant advanced NSCLC.
- To compare these factors between patients with HER2 tyrosine kinase domain (TKD) and non-TKD mutations.
Main Methods:
- Observational study utilizing deidentified data from the Flatiron Health-Foundation Medicine NSCLC Clinico-Genomic Database.
- Inclusion criteria: advanced/metastatic NSCLC with oncogenic HER2 mutations.
- Assessment of mutation prevalence, coaberrations, treatment patterns, and OS.
Main Results:
- 3.8% of patients had HER2 mutations, with 1.8% being oncogenic (n=262).
- Patients with oncogenic TKD mutations (n=197) were younger, more often female, and never-smokers compared to non-TKD (n=65).
- Median OS after first-line treatment was 13.5 months; second-line was 11.1 months. First-line chemoimmunotherapy showed better OS (21.1 months) for TKD vs. non-TKD (11.7 months).
Conclusions:
- HER2-mutant NSCLC patients with TKD mutations exhibit distinct characteristics and genetic profiles compared to non-TKD mutation patients.
- Standard-of-care treatments for advanced HER2-mutant NSCLC yield suboptimal real-world outcomes.
- There is a significant unmet need for novel therapeutic strategies for this patient population.
