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The New England Journal of MedicineNeoadjuvant or Perioperative Approach in Lung Cancer

Exploring the comparative benefits of neoadjuvant and perioperative approaches in early-stage resectable NSCLC, with a focus on the role of immunotherapy and its impact on clinical outcomes.

Recent studies have highlighted the potential benefits of perioperative and neoadjuvant immunotherapy in improving outcomes for patients with early-stage resectable non-small-cell lung cancer (NSCLC). These approaches, which involve administering immunotherapy before and after surgery, have shown promise in reducing the risk of recurrence and enhancing disease-free survival. This editorial reviews key findings from several pivotal trials, including CheckMate 77T, which demonstrate the efficacy of combining immunotherapy with chemotherapy in the perioperative setting.

Key Points:

  • Neoadjuvant and Adjuvant Therapy: Both approaches are effective in reducing recurrence in early-stage resectable NSCLC, with perioperative treatment showing additional benefits.
  • IMpower010 Trial: Atezolizumab post-adjuvant chemotherapy improved disease-free survival in resected stage II-IIIA NSCLC, especially in tumors with >1% PD-L1 expression.
  • PEARLS/Keynote-091 Trial: Pembrolizumab demonstrated disease-free survival benefits in resected stage IB-IIIA NSCLC regardless of PD-L1 expression, but no overall survival benefit was observed.
  • Neoadjuvant Immunotherapy Hypothesis: Administering immunotherapy in the presence of the primary tumor may elicit a stronger immune response, supporting the strategy’s potential.
  • CheckMate 816 Trial: Combining nivolumab with chemotherapy before surgery resulted in significant event-free survival benefits compared to chemotherapy alone.
  • Perioperative Approach Trials: Five phase 3 trials using various PD-1/PD-L1 inhibitors have shown consistent reductions in recurrence risk.
  • Keynote 671 Trial: This trial was the only one to show a significant improvement in overall survival with perioperative pembrolizumab, highlighting its potential.
  • CheckMate 77T Findings: The trial showed a clear event-free survival benefit with perioperative nivolumab and chemotherapy, with a hazard ratio of 0.58 for disease progression or death.
  • Treatment Choice Considerations: Physicians should consider drug availability, cost, and patient preferences when selecting among the different regimens tested.
  • Surgery Cancellations: Approximately 20% of surgeries were canceled due to tumor progression during neoadjuvant therapy.
  • Stage II NSCLC Treatment: Pooled data from trials support neoadjuvant treatment for all resectable stage II and III patients.
  • PD-L1 Expression Impact: Patients with >50% PD-L1 expression derived the most benefit, but even those with <1% expression showed significant improvements.
  • Unresolved Questions: The necessity of continuing immunotherapy for 1 year post-resection remains uncertain, with ongoing research needed to clarify optimal strategies.

“The observed benefits support the use of neoadjuvant treatment for all patients with resectable stage II and stage III disease, emphasizing the importance of multidisciplinary collaboration among surgeons and medical oncologists to define the best strategy for each patient.”

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