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Frequency and outcomes of brain metastases in patients with HER2-mutant lung cancers
Michael Offin1,2, Daniel Feldman1, Ai Ni3
1Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Background:
Mutations in human epidermal growth factor receptor 2 (HER2; also known as ERBB2) are found in approximately 2% of lung adenocarcinomas. The frequency and clinical course of brain metastases in this oncogenic subset are ill defined.
Methods:
Baseline and subsequent development of brain metastases was evaluated in consecutive patients with HER2-mutant (n = 98), epidermal growth factor receptor (EGFR)-mutant (n = 200), and KRAS-mutant lung cancers (n = 200).
Results:
At metastatic diagnosis, the odds ratio (ORs) for brain metastases was similar for patients whose tumors harbored HER2 mutations (19%) in comparison with patients with KRAS mutations (24%; OR for HER2 vs KRAS, 0.7; P = .33) but lower compared to patients with EGFR mutations (31%; OR for HER2 vs EGFR, 0.5; P = .03). Patients with lung cancer and HER2 mutations developed more brain metastases on treatment than patients with KRAS mutations (28% vs 8%; hazard ratio [HR], 5.2; P < .001) and trended more than patients with EGFR mutations (28% vs 16%; HR, 1.7; P = .06). Patients with HER2 YVMA mutations also developed more brain metastases on treatment than patients with KRAS mutations (HR, 5.9; P < .001). The median overall survival (OS) was shorter for patients with HER2-mutant (1.6 years; P < .001) or KRAS-mutant lung cancers (1.1 years; P < .001) than patients with EGFR-mutant lung cancers (3.0 years). Brain metastases occurred in 47% of patients with HER2-mutant lung cancers, which imparted shorter OS (HR, 2.7; P < .001).
Conclusions:
These data provide a framework for brain imaging surveillance in patients with HER2-mutant lung cancers and underpin the need to develop HER2-targeted agents with central nervous system activity.
Insights
Patients with HER2-mutant lung cancer have a high risk of developing brain metastases, impacting overall survival. Further research into HER2-targeted therapies with CNS activity is crucial for this patient group.
Area of Science:
- Oncology
- Genetics
- Neurology
Background:
- Human epidermal growth factor receptor 2 (HER2) mutations occur in about 2% of lung adenocarcinomas.
- The clinical course and frequency of brain metastases in HER2-mutant lung cancer are not well understood.
Purpose of the Study:
- To evaluate the incidence and clinical course of brain metastases in patients with HER2-mutant lung cancer.
- To compare brain metastasis development and survival outcomes between HER2-mutant and other common lung cancer mutation subtypes (EGFR, KRAS).
Main Methods:
- Retrospective analysis of consecutive patients with HER2-mutant (n=98), EGFR-mutant (n=200), and KRAS-mutant (n=200) lung cancers.
- Evaluation of baseline and subsequent development of brain metastases, and overall survival.
Main Results:
- At diagnosis, brain metastasis prevalence was similar for HER2-mutant (19%) and KRAS-mutant (24%) lung cancers, but lower than EGFR-mutant (31%).
- During treatment, HER2-mutant lung cancers showed a significantly higher rate of brain metastases compared to KRAS-mutant (28% vs 8%) and a trend compared to EGFR-mutant (28% vs 16%).
- Patients with HER2-mutant lung cancer had shorter overall survival (1.6 years) compared to EGFR-mutant (3.0 years), with brain metastases further reducing survival (HR, 2.7).
Conclusions:
- HER2-mutant lung cancer patients have a high risk of developing brain metastases, necessitating brain imaging surveillance.
- The development of HER2-targeted therapies with central nervous system activity is critical for improving outcomes in this population.
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