What are the common side effects of Osimertinib (Tagrisso) in non-small cell lung cancer treatment?

Osimertinib Side Effects in NSCLC Treatment

Osimertinib demonstrates a favorable safety profile compared to chemotherapy, with the most common adverse effects being diarrhea (36-58%), rash (39-58%), nail toxicity (23-37%), dry skin (17-36%), and stomatitis (15-32%), though serious grade ≥3 adverse events occur in only 23% of patients. 1

Common Adverse Effects (Occurring in >20% of Patients)

Gastrointestinal Effects

• Diarrhea occurs in 36-58% of patients across different treatment settings, with grade 3-4 events in only 2.1-2.4% 1
• Stomatitis affects 15-32% of patients, with grade 3-4 events in <2% 1
• Decreased appetite occurs in 13-20% of patients 1

Dermatologic Effects

• Rash is reported in 39-58% of patients, but severe (grade 3-4) rash occurs in only 0.7-1.1% 1
• Nail toxicity (paronychia, nail bed disorders) affects 23-37% of patients, with grade 3-4 events in <1% 1
• Dry skin occurs in 17-36% of patients, with minimal severe events 1
• Pruritus affects 13-19% of patients 1

Hematologic Abnormalities

• Lymphopenia is the most common laboratory abnormality, occurring in 44-70% of patients, though grade 3-4 events occur in only 3.4-3.5% 1
• Leukopenia affects 54-66% of patients, with grade 3-4 events in <3% 1
• Thrombocytopenia occurs in 47-51% of patients, with grade 3-4 events in 1.4% 1
• Neutropenia affects 26-42% of patients, with grade 3-4 events in 2.1% 1

Serious but Less Common Adverse Effects

Pulmonary Toxicity

• Interstitial lung disease (ILD)/pneumonitis is the most clinically significant adverse effect, occurring in 3.9-56% depending on treatment setting (higher rates in post-radiation settings) 2, 1
• In the LAURA trial (post-chemoradiation), ILD/pneumonitis occurred in 56% of patients, with grade 3-4 events in 3.5% 1
• Fatal events from pneumonitis have been reported, including 2 respiratory failure deaths and 1 pneumonitis death in clinical trials 2

Cardiac Toxicity

• QTc prolongation occurs in 0.7-10% of patients, with grade 3-4 events in 0.7-2.2% 1
• The National Comprehensive Cancer Network recommends that patients with mean resting QTc >470 msec should not receive osimertinib 3
• Concomitant QT-prolonging medications should be discontinued or substituted before initiating osimertinib 3
• One fatal ischemic stroke was reported in clinical trials 2

Other Serious Events

• Pneumonia occurs in 10-15% of patients, with grade 3-4 events in 3.5-5% 1
• Fatal events from pneumonia have been documented 2

Comparative Safety Profile

Osimertinib demonstrates superior tolerability compared to platinum-based chemotherapy, with significantly fewer grade ≥3 adverse events (23% vs 47%). 2

Versus Chemotherapy

• Grade ≥3 adverse events: 23% with osimertinib vs 47% with chemotherapy 2
• Osimertinib causes more diarrhea, rash, and nail toxicity, while chemotherapy causes more cytopenias, nausea, and appetite loss 2

Versus Other EGFR TKIs

• Osimertinib has a similar overall adverse event profile to first-generation EGFR TKIs (gefitinib, erlotinib) but with better CNS penetration 2
• Afatinib (second-generation TKI) has higher rates of severe diarrhea (13% vs 2.2% grade 3-4) and is rated as less safe than osimertinib 2

Treatment Discontinuation and Dose Modifications

• Permanent discontinuation due to adverse events occurs in 13% of patients, most commonly due to ILD/pneumonitis (3.9-7%) 1
• Dose reductions occur in 2.9-8% of patients, most frequently for QT prolongation, diarrhea, and lymphopenia 1
• Dose interruptions occur in 56% of patients in post-radiation settings, primarily for ILD/pneumonitis (35%) 1

Critical Safety Monitoring

Mandatory Assessments

• Baseline and periodic ECG monitoring for QTc prolongation, especially in patients with cardiac risk factors 3
• Review and minimize concurrent QT-prolonging medications 3
• Monitor for signs/symptoms of ILD/pneumonitis, particularly in patients receiving osimertinib after chemoradiation 1
• Regular complete blood counts to monitor for cytopenias 1

High-Risk Populations

• Patients with baseline QTc >470 msec should not receive osimertinib 3
• Patients receiving osimertinib after definitive chemoradiation have significantly higher rates of ILD/pneumonitis (56% vs 3.9% in treatment-naive patients) 1

Patient-Reported Experience

Patients report high satisfaction with osimertinib and low difficulty coping with side effects, with most symptoms rated as low-to-moderate in bothersomeness. 4

• At 4-6 weeks: most common symptoms are coughing (56.5%), itching (56.5%), tiredness (56.5%), and rash (43.5%) 4
• At 4 months: shortness of breath and diarrhea increase, while itching, coughing, and rash decrease 4
• Rarely reported symptoms (abdominal pain, urinary frequency) may receive high bothersomeness ratings when present 4