What are the indications for adjuvant treatment in patients with Epidermal Growth Factor Receptor (EGFR) positive Non-Small Cell Lung Cancer (NSCLC) who have undergone surgical resection?

Indications for Adjuvant Treatment in EGFR-Positive Lung Cancer

Osimertinib 80 mg daily for 3 years is the recommended adjuvant therapy for completely resected stage IB-IIIA EGFR-mutant NSCLC (exon 19 deletions or L858R mutations), and adjuvant platinum-based chemotherapy should also be administered regardless of osimertinib use for stage IB-IIIA disease with good performance status. 1

Primary Indication: Adjuvant Osimertinib

Osimertinib is indicated for:

• Stage IB-IIIA (7th AJCC TNM edition) completely resected NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations 1, 2
• Duration: 3 years of continuous therapy at 80 mg once daily until disease recurrence, unacceptable toxicity, or completion of 3 years 1, 2
• Impressive disease-free survival benefit: HR 0.17 for stage II-IIIA disease and HR 0.20 for overall stage IB-IIIA population 1, 3
• Superior CNS disease control: HR 0.18 for CNS disease-free survival 1, 3

Evidence Supporting Osimertinib

The ADAURA trial demonstrated dramatic improvements in disease-free survival that distinguish osimertinib from prior failed attempts with first- and second-generation EGFR TKIs 1, 3. At 24 months, 90% of stage II-IIIA patients receiving osimertinib remained disease-free compared to only 44% receiving placebo 3. This benefit was observed regardless of whether patients received adjuvant chemotherapy 1, 4.

Adjuvant Chemotherapy Remains Essential

Platinum-based adjuvant chemotherapy is strongly recommended for:

• Stage IB-IIIA EGFR-mutant NSCLC with good performance status 1
• High-risk stage IB disease (margin-negative) may also be considered 1
• Should be given regardless of osimertinib administration 1

The chemotherapy recommendation is based on decades of evidence showing survival benefit in resected NSCLC 1. In ADAURA, approximately 60% of patients received adjuvant chemotherapy, and osimertinib benefit was maintained in both chemotherapy-treated and chemotherapy-naive subgroups 1, 4.

What NOT to Use

First- and second-generation EGFR TKIs (erlotinib, gefitinib) are NOT recommended in the adjuvant setting 1:

• Multiple phase III trials (RADIANT, CTONG-1104, IMPACT, BR.19) failed to demonstrate overall survival benefit 1
• Initial disease-free survival advantages disappeared approximately 2 years after TKI discontinuation 1
• CTONG-1104 showed DFS benefit (HR 0.56) but no OS benefit (HR 0.92) 1
• IMPACT was negative for both DFS (HR 0.92) and OS (HR 1.03) 1

Stage III Unresectable Disease

For stage IIIB unresectable NSCLC following platinum-based chemoradiation without progression:

• Osimertinib 80 mg daily may be offered for EGFR exon 19 deletion or L858R mutation-positive disease 1, 5, 2
• This is distinct from the adjuvant post-resection indication 1, 5

Critical Follow-Up Requirements

Enhanced surveillance is mandatory for EGFR-mutant resected NSCLC 1:

• Brain MRI every 6 months (preferred over CT) due to higher CNS metastasis risk 1
• Chest/upper abdomen CT every 4-6 months for at least 2 years, then consider continuing beyond standard 2-year window 1
• Early detection of CNS disease allows for stereotactic radiosurgery intervention 1

Common Pitfalls to Avoid

Do not:

• Use first- or second-generation EGFR TKIs as adjuvant therapy—they lack survival benefit 1
• Omit adjuvant chemotherapy in eligible patients receiving osimertinib—both should be given 1
• Follow standard NSCLC surveillance protocols without adding brain imaging—EGFR-mutant disease requires CNS-specific monitoring 1
• Confuse stage IIIB unresectable (consolidation after chemoradiation) with resected stage IB-IIIA (adjuvant post-surgery) indications 1, 5, 2

Important Caveats

Overall survival data remain immature from ADAURA, with only 29 deaths at initial analysis 1, 3. While the disease-free survival benefit is impressive (HR 0.17-0.20), confirmation of overall survival benefit and quality of life data upon mature follow-up would strengthen the recommendation 1. However, the magnitude of DFS benefit, superior CNS control, and longer treatment duration (3 vs 2 years) distinguish osimertinib from failed prior adjuvant TKI trials 1.

The safety profile was manageable with no new safety signals, and most adverse events were grade 1-2 (rash, diarrhea, nail toxicity) 3, 6.