Osimertinib, also known by its brand name Tagrisso, represents a significant advancement in the treatment of a specific type of lung cancer. It is a targeted therapy designed to address non-small cell lung cancer (NSCLC) that carries particular genetic alterations. This specialized medication aims to block signals that promote cancer cell growth, offering a more precise approach compared to traditional chemotherapy.
Understanding EGFR-Mutated Lung Cancer
Lung cancer is a broad term, but osimertinib specifically targets a subtype known as non-small cell lung cancer, which accounts for the majority of lung cancer cases. A significant step in managing NSCLC involves genetic testing, also referred to as biomarker testing. This testing identifies specific changes or mutations within a tumor’s DNA.
One of the most common mutations found in NSCLC is in the Epidermal Growth Factor Receptor (EGFR) gene. EGFR is a protein on cell surfaces that normally helps cells grow and divide, but mutations can cause it to become overactive, leading to uncontrolled cell growth and cancer.
Identifying these EGFR mutations, particularly exon 19 deletions and the L858R point mutation in exon 21, indicates that the cancer may respond to targeted therapies like osimertinib. These mutations are more prevalent in adenocarcinomas and can be found in approximately 10-20% of NSCLC cases in Western populations and up to 50% in Asian populations.
How Osimertinib Targets Lung Cancer
Osimertinib is classified as a third-generation tyrosine kinase inhibitor (TKI), a type of drug that works by blocking specific enzymes involved in cell signaling pathways. Unlike earlier generations of TKIs, osimertinib is designed to selectively target common EGFR mutations, including exon 19 deletions and the L858R mutation in exon 21. It also specifically targets the T790M resistance mutation, which often develops in patients who have previously been treated with first- or second-generation EGFR TKIs and whose cancer has become resistant to those treatments.
The drug works by irreversibly binding to the mutated EGFR protein. This binding action effectively blocks the signals that drive the uncontrolled growth and survival of cancer cells. By targeting these specific mutations, osimertinib helps to slow down or stop the growth of the cancer, while minimizing its effects on healthy cells that have normal EGFR. This selective action can lead to a more favorable safety profile compared to less selective therapies.
When Osimertinib is Prescribed
Osimertinib is used in several different clinical situations for patients with EGFR-mutated non-small cell lung cancer. It is commonly prescribed as a first-line treatment for patients newly diagnosed with locally advanced or metastatic EGFR-mutated NSCLC. Clinical studies have shown that osimertinib can lead to longer progression-free survival and overall survival compared to earlier-generation EGFR TKIs in this setting.
The medication is also used for patients whose cancer has progressed after receiving earlier EGFR TKI therapies and who have developed the T790M resistance mutation. Additionally, osimertinib has a role in adjuvant therapy, meaning it can be given after surgery for patients with earlier-stage (IB to IIIA) EGFR-mutated NSCLC to help prevent the cancer from returning. Osimertinib is administered as an oral tablet, typically taken once a day, making it a convenient treatment option for patients.
Managing Treatment Side Effects
Like all medications, osimertinib can cause side effects, though it is well-tolerated compared to traditional chemotherapy. Common side effects include diarrhea, skin rash, and changes to nails. The skin rash may appear acne-like, red, or dry, and patients are often advised to use alcohol-free moisturizing creams and avoid excessive sun exposure.
Nail changes, such as inflammation around the nail bed or nail ridging, can also occur. Patients are encouraged to keep nails clean and dry and avoid cutting cuticles. Diarrhea can often be managed with over-the-counter medications like loperamide and by maintaining hydration with fluids containing sugar and salt, while avoiding caffeinated or alcoholic beverages.
Fatigue is another common symptom, which can be managed by balancing rest and activity. Patients are advised to promptly report any new or worsening symptoms to their healthcare team for appropriate management and to ensure treatment continues safely.