Tagrisso, known scientifically as osimertinib, is a targeted therapy for specific forms of non-small cell lung cancer (NSCLC). Its use is determined by the presence of distinct genetic markers within cancer cells, as the drug’s effectiveness is linked to a tumor’s unique genetic profile. This article explores the relationship between Tagrisso and an EGFR exon 20 insertion, examining its role in lung cancer treatment.
Understanding EGFR Exon 20 Insertion Mutations
The epidermal growth factor receptor (EGFR) is a protein on the surface of cells that functions like a switch, receiving signals that tell cells when to grow and divide. An “exon 20 insertion” is a specific type of mutation where extra genetic material is added into a particular region of the EGFR gene, which changes how the protein works.
This insertion jams the EGFR protein’s switch into the “on” position, leading to constant, uncontrolled cell growth. Historically, this specific class of mutations has been more difficult to treat with earlier generations of targeted therapies. While other EGFR mutations responded well to initial treatments, the unique structural change caused by exon 20 insertions made the cancer cells resistant to them.
Detecting these mutations requires specialized genomic testing, which can be performed on a tumor tissue sample obtained through a biopsy. A less invasive method known as a liquid biopsy analyzes a blood sample for fragments of cancer DNA. Identifying the exact type of EGFR mutation is required to determine the most appropriate course of treatment for a patient with NSCLC.
Tagrisso’s Role in Treating Exon 20 Mutations
Tagrisso is a tyrosine kinase inhibitor (TKI) engineered to block signals from the mutated EGFR protein. By binding to this protein, it prevents the signaling that drives cell proliferation, helping to control cancer growth. The drug is widely used for common EGFR mutations, such as exon 19 deletions and the L858R substitution.
Tagrisso’s role concerning EGFR exon 20 insertion mutations is more complex. It has shown limited activity against most exon 20 insertion variants when used alone. The structural alteration in the EGFR protein caused by these insertions often prevents the drug from binding effectively. For this reason, its application for exon 20 insertions is not part of its standard FDA indication, and its use is considered off-label or within a clinical trial.
Research is exploring its potential in combination with other drugs. For instance, a phase 2 study investigated Tagrisso combined with becotarug for patients with EGFR exon 20 insertion-positive NSCLC who had progressed after chemotherapy. This combination showed an objective response rate of 50%, meaning half of the patients experienced a significant reduction in their tumor size. The median progression-free survival was 6.9 months with this combination.
Potential Side Effects of Tagrisso
Like all medications, treatment with Tagrisso is associated with potential side effects that can range from mild to severe. Patients are encouraged to maintain open communication with their healthcare providers to report any adverse effects, as many can be managed with supportive care or dose adjustments.
Frequently observed side effects include gastrointestinal and dermatologic issues. Common problems can include:
- Diarrhea
- Skin-related problems such as rash and dry skin
- Nail toxicity affecting fingernails and toenails
- Fatigue
- Stomatitis (soreness in the mouth)
- Decreased blood cell counts (leukopenia and thrombocytopenia)
Less commonly, Tagrisso can lead to more serious health concerns. One is a lung condition known as pneumonitis or interstitial lung disease, which involves inflammation of the lung tissue and can cause coughing and shortness of breath. Heart-related issues can also arise, including cardiomyopathy (weakening of the heart muscle) and QTc prolongation, an electrical disturbance that can affect heart rhythm. Promptly reporting any new or worsening symptoms is necessary for patient safety.
Alternative and Combination Treatment Strategies
Given the challenges of treating EGFR exon 20 insertion mutations with Tagrisso alone, other therapeutic avenues are often pursued. The treatment landscape for this subtype of NSCLC has led to the approval of drugs designed specifically for this mutation. One such targeted therapy is amivantamab (Rybrevant), an antibody that targets both EGFR and another protein called MET.
Another targeted therapy, mobocertinib, was previously an option but was voluntarily withdrawn from the market. Chemotherapy also remains an effective treatment for patients with this mutation. It is often used as a first-line treatment or after a targeted therapy stops working.
Clinical trials are a pathway for patients to access new treatments, and they often investigate novel drugs or new combinations of existing ones. Research is ongoing to evaluate different TKIs and drug combinations that may be more effective for exon 20 insertions. Participation can provide access to a potentially more beneficial therapy.