Neoadjuvant PD-1 Blockade in Resectable Lung Cancer

Area of Science:

• Oncology
• Immunotherapy
• Surgical Oncology

Background:

• Programmed death 1 (PD-1) inhibitors improve survival in advanced non-small-cell lung cancer (NSCLC).
• Limited progress has been made in treating resectable NSCLC over the past decade.
• The efficacy of PD-1 blockade in resectable NSCLC has not been previously investigated.

Purpose of the Study:

• To assess the safety and feasibility of neoadjuvant PD-1 inhibitor nivolumab in patients with resectable NSCLC.
• To evaluate the pathological response to neoadjuvant nivolumab.
• To explore the relationship between tumor mutational burden, PD-L1 expression, and T-cell responses following PD-1 blockade.

Main Methods:

• Pilot study administering two preoperative doses of nivolumab (3 mg/kg) every 2 weeks to adults with resectable early-stage NSCLC.
• Surgery was planned approximately 4 weeks after the first dose.
• Evaluated safety, feasibility, tumor pathological response, PD-L1 expression, mutational burden, and T-cell responses.

Main Results:

• Neoadjuvant nivolumab demonstrated an acceptable side-effect profile and did not delay surgery.
• A major pathological response was observed in 45% (9 of 20) of resected tumors, irrespective of PD-L1 expression.
• A significant correlation was found between pathological response and pretreatment tumor mutational burden.
• PD-1 blockade led to systemic expansion of mutation-associated, neoantigen-specific T-cell clones in peripheral blood.

Conclusions:

• Neoadjuvant nivolumab is safe and feasible for resectable NSCLC, inducing significant pathological responses.
• Tumor mutational burden is a predictive biomarker for pathological response to PD-1 blockade.
• Nivolumab treatment stimulates systemic T-cell responses against neoantigens.