What is the treatment approach for lung cancer, specifically in relation to the Aegean trial?

Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer: The AEGEAN Trial Approach

Perioperative durvalumab plus neoadjuvant chemotherapy is the preferred treatment approach for resectable stage II-IIIB non-small-cell lung cancer (NSCLC) based on the AEGEAN trial, which demonstrated significantly improved event-free survival and pathological complete response rates compared to chemotherapy alone. 1

AEGEAN Trial Results and Implications

• The AEGEAN trial was a phase III, double-blind, placebo-controlled study evaluating durvalumab (a PD-L1 inhibitor) plus platinum-based chemotherapy before surgery, followed by adjuvant durvalumab in patients with resectable stage II-IIIB NSCLC 2, 1

• Key findings from the AEGEAN trial showed:

  • Significantly longer event-free survival with durvalumab compared to placebo (hazard ratio 0.68; 95% CI, 0.53 to 0.88; P = 0.004) 1
  • Higher pathological complete response rate with durvalumab (17.2% vs. 4.3%; difference of 13.0 percentage points; P<0.001) 1
  • Benefits observed regardless of disease stage and PD-L1 expression levels 1
  • Similar safety profile between durvalumab and placebo arms (grade 3-4 adverse events: 42.4% vs. 43.2%) 1

Treatment Algorithm for Resectable NSCLC

Initial Assessment and Staging

• Complete history including smoking history, comorbidities, weight loss, performance status, and physical examination 3
• Contrast-enhanced CT scan of chest and upper abdomen for initial imaging 3
• PET-CT scan for mediastinal lymph nodes and distant metastasis assessment 3
• Brain imaging (preferably MRI) for patients eligible for loco-regional treatment 3
• Pathological confirmation of suspect nodes via needle aspiration under endobronchial/endoscopic ultrasound guidance 3

Treatment Approach Based on Stage

For Resectable Stage II-IIIB NSCLC:

• First choice: Perioperative approach with durvalumab plus platinum-based chemotherapy (4 cycles) before surgery, followed by adjuvant durvalumab for 12 cycles 1
• The perioperative immunotherapy approach combines the benefits of both neoadjuvant and adjuvant strategies to improve long-term outcomes 1

For Stage I NSCLC:

• Anatomical resection (lobectomy) is preferred over lesser resections 3
• For patients unfit for surgery, stereotactic ablative radiotherapy (SABR) is the non-surgical treatment of choice 3
• Sub-lobar resection may be considered for pure ground-glass opacity lesions or adenocarcinomas in situ 3

For Locally Advanced Stage III (Unresectable):

• Definitive concurrent chemotherapy and radiotherapy is the preferred treatment 3
• Cisplatin-based regimens (e.g., cisplatin-etoposide or cisplatin-vinorelbine) delivered concurrently with radiotherapy are recommended 3

For Stage IV Disease:

• Two-drug, platinum-based chemotherapy combined with vinorelbine, gemcitabine, or a taxane for patients with good performance status 3
• For non-squamous tumors, cisplatin should be the treatment of choice 3
• Pemetrexed is preferred to gemcitabine in patients with non-squamous tumors 3

Special Considerations

EGFR Mutation-Positive NSCLC

• For patients with EGFR mutation-positive NSCLC, osimertinib has demonstrated efficacy in the adjuvant setting 4
• First-line treatment with a TKI (erlotinib or gefitinib) should be prescribed to patients with tumors bearing an activating EGFR mutation 3

Performance Status Considerations

• For patients with PS 2, single-agent chemotherapy with gemcitabine, vinorelbine, or taxanes represents an option, though platinum-based combinations may also be considered 3
• Poor PS (3-4) patients should be offered best supportive care in the absence of tumors with activating EGFR mutations 3

Follow-Up Recommendations

• Follow-up visits every 3-6 months during the first 2-3 years, then annually thereafter 3
• History and physical examination, chest CT, and to a lesser extent, chest X-ray are appropriate follow-up tools 3
• Smoking cessation should be offered to all patients, as this leads to superior treatment outcomes 3

Caveats and Pitfalls

• Patients with documented EGFR or ALK alterations were excluded from the efficacy analyses in the AEGEAN trial, so the perioperative durvalumab approach may not be optimal for these patients 1
• Despite improvements in diagnosis and therapy, the prognosis for patients with lung cancer remains challenging, requiring a multidisciplinary team approach 5, 6
• Careful assessment of cardiac and pulmonary function is necessary before considering surgical resection to estimate risk of operative morbidity 3