1. Cardiopulmonary Effects: Some TKIs, including Osimertinib, may have cardiovascular effects. Long-term use may be associated with a risk of heart-related issues, such as QT interval prolongation or interstitial lung disease. Regular cardiac monitoring may be recommended.

2. Drug Resistance: Over time, cancer cells may develop resistance to Osimertinib, leading to disease progression. This is a consideration for long-term treatment, and healthcare providers may need to reassess the treatment plan.

3. Skin and Nail Changes: Cutaneous side effects, such as skin rash, dry skin, and changes in the nails, can occur with Osimertinib. These effects may persist during long-term treatment.

4. Gastrointestinal Issues: Some patients may experience gastrointestinal side effects, including diarrhea and nausea. Managing these symptoms is important for the patient's quality of life during long-term use.

5. Liver Enzyme Abnormalities: Osimertinib can affect liver function, leading to increased levels of liver enzymes. Regular monitoring of liver function is typically conducted during treatment.

6. Endocrine Effects: Osimertinib may affect the endocrine system, leading to changes in glucose metabolism. Blood glucose levels should be monitored, especially in patients with diabetes or at risk of diabetes.

It's important to emphasize that the benefits of Osimertinib, including its efficacy in treating specific EGFR-mutated NSCLC, are crucial considerations in the decision-making process. Healthcare providers carefully weigh the potential benefits against the risks and side effects when prescribing and continuing long-term treatment with Osimertinib.