What to monitor in patients on Osimertinib (osimertinib)?

From the Guidelines

Patients on Osimertinib should be monitored for signs of pneumonitis, as it is a known side effect of the medication.

Monitoring Parameters

• Pneumonitis: as osimertinib is associated with a risk of pneumonitis, patients should be monitored for symptoms such as cough, dyspnea, and fever 1
• Ischemic stroke: osimertinib may also increase the risk of ischemic stroke, and patients should be monitored for signs of stroke, such as sudden weakness or numbness in the face, arm, or leg 1
• Resistance mechanisms: patients on osimertinib should be monitored for the development of resistance mechanisms, such as EGFR mutations (e.g. p.C797S, p.L718Q, p.L792F, and p.G796S) or MET amplification, which can occur in 10-15% of patients 1
• CNS metastases: osimertinib has shown efficacy in patients with CNS metastases, and patients should be monitored for signs of CNS progression, such as headaches, seizures, or changes in mental status 1

Laboratory Tests

• Plasma genotyping: may be considered to detect the presence of EGFR mutations, such as T790M, which can inform treatment decisions 1
• Tumor biopsy: may be necessary to confirm the presence of EGFR mutations or other resistance mechanisms, and to guide treatment decisions 1

Clinical Assessment

• Patients should be regularly assessed for signs of disease progression, such as increased symptoms, or changes in performance status 1
• Patients with slow disease progression and no deterioration in clinical symptoms may be considered for continuation of osimertinib until symptomatic or significant progression 1

From the FDA Drug Label

Over the same dose range, increased exposure led to increased probability of adverse reactions, specifically rash, diarrhea and ILD. Cardiac Electrophysiology The QTc interval prolongation potential of osimertinib was assessed in 210 patients who received TAGRISSO 80 mg daily in AURA2 The patient on Osimertinib should be monitored for:

• Rash
• Diarrhea
• Interstitial Lung Disease (ILD)
• QTc interval prolongation 2

From the Research

Monitoring Parameters for Patients on Osimertinib

To ensure safe and effective treatment with osimertinib, several parameters should be monitored:

• Cardiac function:
  • Electrocardiogram (ECG) abnormalities 3, 4, 5, 6
  • Heart failure (HF) 3, 4, 5, 6
  • Atrial fibrillation 3, 4, 5, 6
  • QT prolongation 3, 4, 5, 6
• Cardiovascular risk factors:
  • Hypertension 3, 4, 6
  • History of cardiovascular disease 3, 4, 6
• Other parameters:
  • Liver function tests (not specified in the provided studies)
  • Renal function tests (not specified in the provided studies)

Recommended Monitoring Schedule

The frequency of monitoring should be based on individual patient risk factors and medical history. However, the following schedule can be considered:

• Baseline assessment: before starting osimertinib treatment
• Regular monitoring: every 3-6 months during treatment, or more frequently if cardiac risk factors are present
• As-needed monitoring: if symptoms or signs of cardiotoxicity occur

Therapeutic Drug Monitoring

Therapeutic drug monitoring (TDM) may be useful to optimize osimertinib dosing and minimize adverse effects. A validated UPLC-MS/MS method is available for simultaneous quantification of osimertinib, aumolertinib, and furmonertinib in human plasma 7. However, the clinical utility of TDM for osimertinib has not been established.