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Positive progress for non-small cell lung cancer with epidermal growth factor receptor exon 20 insertion mutations: A
1Department of Geriatrics, 117865Tianjin Medical University General Hospital, People's Republic of China.
Abstract:
Epidermal growth factor receptor gene exon 20 insertion mutations are seen in ∼4-12% of patients with epidermal growth factor receptor-mutant non-small cell lung cancer. However, there is no targeted therapy approved for the treatment of non-small cell lung cancer patients with these rare epidermal growth factor receptor mutations. Previous studies revealed that epidermal growth factor receptor gene exon 20 insertion mutations are unique in their ability to activate epidermal growth factor receptor without the typical structural changes associated with the common epidermal growth factor receptor mutations, reducing the clinical efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors currently approved for non-small cell lung cancer. Therefore, there is an urgent need to identify active epidermal growth factor receptor-tyrosine kinase inhibitors and other effective treatment strategies for non-small cell lung cancer patients with epidermal growth factor receptor gene exon 20 insertion mutations. Mobocertinib is a novel irreversible epidermal growth factor receptor-tyrosine kinase inhibitor that selectively targets epidermal growth factor receptor gene exon 20 insertion mutations. Preclinical study revealed that mobocertinib inhibited the viability of epidermal growth factor receptor gene exon 20 insertion mutations-driven patient-derived xenografts and murine orthotopic tumors more potently than traditional epidermal growth factor receptor-tyrosine kinase inhibitors. In a study recently published in Cancer Discovery, Gonzalvez et al. assessed the safety, tolerability, and antitumor efficacy of mobocertinib in metastatic non-small cell lung cancer patients with epidermal growth factor receptor gene exon 20 insertion mutations. They found that non-small cell lung cancer patients with epidermal growth factor receptor gene exon 20 insertion mutations can benefit from mobocertinib treatment. Additionally, the treatment-related toxicity of mobocertinib was manageable. These findings lay the foundation for the application of mobocertinib in epidermal growth factor receptor gene exon 20 insertion-mutated non-small cell lung cancer.
Insights
Mobocertinib shows promise for treating non-small cell lung cancer with rare EGFR exon 20 insertions. This targeted therapy is effective and manageable for patients lacking other treatment options.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Epidermal growth factor receptor (EGFR) exon 20 insertion mutations occur in 4-12% of non-small cell lung cancer (NSCLC) patients.
- These mutations confer resistance to existing EGFR-tyrosine kinase inhibitors (TKIs) approved for NSCLC.
- There is a critical unmet need for targeted therapies for NSCLC with EGFR exon 20 insertion mutations.
Purpose of the Study:
- To assess the safety, tolerability, and antitumor efficacy of mobocertinib in patients with metastatic NSCLC harboring EGFR exon 20 insertion mutations.
- To evaluate mobocertinib as a novel, irreversible EGFR-TKI targeting these specific mutations.
Main Methods:
- A clinical study evaluated mobocertinib in patients with metastatic NSCLC and EGFR exon 20 insertion mutations.
- Preclinical studies demonstrated mobocertinib's potent inhibition of EGFR exon 20 insertion mutation-driven tumors.
- Assessed safety, tolerability, and antitumor responses to mobocertinib treatment.
Main Results:
- Mobocertinib demonstrated antitumor efficacy in patients with NSCLC and EGFR exon 20 insertion mutations.
- The treatment-related toxicity of mobocertinib was found to be manageable.
- Preclinical data showed mobocertinib's superior inhibition of xenografts and tumors driven by EGFR exon 20 insertion mutations compared to traditional EGFR-TKIs.
Conclusions:
- Mobocertinib offers a potential therapeutic benefit for NSCLC patients with EGFR exon 20 insertion mutations.
- The findings support the further investigation and application of mobocertinib in this patient population.
- Mobocertinib represents a promising targeted therapy for a previously difficult-to-treat subset of NSCLC.
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