EGFR+ lung cancer is a form of lung cancer that is not linked to smoking, caused by specific nonhereditary gene mutations. One of these mutations, exon 20, was previously treated with only chemotherapy until the approval of Mobocertinib, a tyrosine kinase inhibitor, in 2021. However, the drug has since been withdrawn from use in the United States, with the United Kingdom planning to follow suit. This has raised concerns among EGFR+ lung cancer patients in the UK, as they may be left with no treatment options after chemotherapy.
While most lung cancer cases are due to smoking, a significant number of cases are non-smoking related, particularly non-small cell lung cancers caused by mutations in the epidermal growth factor receptor (EGFR), known as EGFR+ lung cancers. These cancers present with atypical symptoms and are often seen in younger individuals. Various nonhereditary mutations can lead to EGFR+ lung cancer, with the exon 20 insertion mutation being the third most common cause, responsible for up to 10% of cases. Unfortunately, there were no effective treatments available for this mutation until the approval of mobocertinib in 2021.
Mobocertinib was the first tyrosine kinase inhibitor designed specifically to target uncommon EGFR mutations, such as the exon 20 insertion mutation. Initial clinical trials showed promising results, with the drug being well-tolerated, halting cancer progression, and improving survival rates for patients with this mutation. However, the manufacturer voluntarily withdrew the drug from use in the US due to its failure to meet primary endpoints in later phase 3 trials, despite having no significant safety concerns. This decision has left many patients without a viable treatment option post-chemotherapy.
Professionals like Prof. Siow Ming Lee emphasize the unmet need for effective treatments for EGFR+ exon 20 insertion mutations, highlighting the potential benefits of drugs like mobocertinib for this specific patient group. Dr. Gini Harrison, a research trustee and survivor of EGFR+ lung cancer, expressed concerns over the withdrawal of mobocertinib, as it will significantly impact patients who rely on this drug. She pointed out that the decision to withdraw the drug was based on clinical trial outcomes rather than safety concerns, leaving patients with fewer treatment options to extend their lives.
While there are alternatives to mobocertinib in the US, the situation is more challenging in the UK, where it is the only treatment funded by the National Health Service for exon 20 patients. Another potentially effective drug, amivantamab, is available privately but not covered by the NHS due to cost considerations. Dr. Harrison called for expedited approval processes to make amivantamab accessible to NHS patients, especially in cases where drug withdrawals leave critical treatment gaps for patients. It is crucial to address these challenges to ensure that patients with EGFR+ lung cancer have access to effective and affordable treatments to improve their quality of life and outcomes.
