What are the treatment options for non-small cell lung cancer (NSCLC)?

Treatment Options for Non-Small Cell Lung Cancer (NSCLC)

The treatment of non-small cell lung cancer (NSCLC) should be based on histology, molecular pathology, disease stage, performance status, and comorbidities, with platinum-based chemotherapy as the backbone for advanced disease, targeted therapies for specific mutations, and immunotherapy for eligible patients. 1

Treatment by Disease Stage

Early-Stage NSCLC (Stage I and II)

• Surgical resection is the preferred treatment for patients with stage I or II NSCLC who can tolerate the procedure 2

  • Anatomical resection (lobectomy) is preferred over lesser resections 2
  • Lymph node dissection should conform to IASLC specifications 2

• Adjuvant chemotherapy

  • Should be offered to patients with resected stage II or III NSCLC 2
  • Can be considered in patients with resected stage IB disease and primary tumor >4 cm 2
  • A two-drug combination with cisplatin is preferable (typically cisplatin-vinorelbine) 2

• Stereotactic ablative radiotherapy (SABR)

  • Treatment of choice for stage I NSCLC in non-surgical candidates 2
  • Dose should be to a biologically equivalent tumor dose of ≥100 Gy 2
  • Associated with low toxicity in patients with COPD and the elderly 2

Locally Advanced NSCLC (Stage III)

• Concurrent chemoradiotherapy is the preferred treatment for unresectable stage III NSCLC 2, 1

  • Cisplatin-based regimens (cisplatin-etoposide or cisplatin-vinorelbine) delivered concurrently with radiotherapy are recommended 2
  • Definitive thoracic radiotherapy should be no less than the biological equivalent of 60 Gy in 2.0 Gy fractions 2

• Sequential chemoradiotherapy

  • Option for patients unfit for concurrent approach 2
  • A platinum-based two-drug combination is preferred, with 2-4 cycles 2

Advanced/Metastatic NSCLC (Stage IV)

• Molecular testing is essential to guide treatment decisions 2, 1

  • EGFR mutation testing for all non-squamous NSCLC 2
  • ALK rearrangement testing, particularly in never/light smokers 2
  • PD-L1 expression testing for immunotherapy eligibility 1

• First-line treatment options:

  1. Targeted therapy:

     • EGFR TKIs (erlotinib, gefitinib) for tumors with activating EGFR mutations 2, 1
     • Crizotinib for ALK-rearranged tumors 2, 1

  2. Immunotherapy:

     • Single-agent pembrolizumab for PD-L1 ≥50% 1, 3
     • Pembrolizumab with chemotherapy for non-squamous NSCLC regardless of PD-L1 status 3

  3. Chemotherapy:

     • Platinum-based combinations for patients without driver mutations 2
     • For non-squamous histology: cisplatin preferred over carboplatin 2
     • Pemetrexed preferred over gemcitabine for non-squamous tumors 2
     • Bevacizumab can be added to platinum-based chemotherapy in eligible patients with non-squamous histology 2

• Maintenance therapy:

  • Pemetrexed switch maintenance for non-squamous histology 2
  • Erlotinib maintenance for patients with stable disease after induction treatment 2

• Second-line treatment:

  • Docetaxel with or without ramucirumab for patients who progress after first-line chemotherapy 1, 4
  • Immunotherapy (nivolumab, pembrolizumab, atezolizumab) after progression on first-line therapy 1

Special Patient Populations

Poor Performance Status (PS ≥2)

• Single-agent chemotherapy (gemcitabine, vinorelbine, taxanes) for PS 2 2
• Platinum-based combinations may be considered as an alternative for PS 2 2
• Best supportive care for PS 3-4 patients 2, 1
• Exception: EGFR TKIs may be offered to PS 3-4 patients with EGFR mutations 2

Elderly Patients

• Single-agent chemotherapy is standard for clinically unselected elderly patients 2
• Platinum-based chemotherapy for elderly patients with PS 0-1 and adequate organ function 2
• Consider comorbidities and increased risk of treatment-related adverse events 2

Important Considerations

• Smoking cessation should be strongly encouraged as it improves treatment outcomes 2, 1
• Treatment decisions should be discussed within a multidisciplinary tumor board 2, 1
• Regular follow-up is recommended at least every 6 weeks after first-line therapy 1
• In all stages of NSCLC, best supportive care should be integrated into treatment plans 1

Common Pitfalls to Avoid

• Using EGFR TKIs in EGFR wild-type patients as first-line therapy (inferior to chemotherapy) 2
• Extending first-line chemotherapy beyond 4-6 cycles (no survival benefit, increased toxicity) 2
• Neglecting molecular testing before initiating treatment 2, 1
• Overlooking the importance of performance status in treatment selection 2
• Failing to consider histology-specific treatment approaches (squamous vs. non-squamous) 2