Five-Year Clinical Outcomes after Neoadjuvant Nivolumab in Resectable Non-Small Cell Lung Cancer

• Published in: Clinical cancer research Vol. 29; no. 4; p. 705
• Main Authors: Rosner, Samuel, Reuss, Joshua E, Zahurak, Marianna, Zhang, Jiajia, Zeng, Zhen, Taube, Janis, Anagnostou, Valsamo, Smith, Kellie N, Riemer, Joanne, Illei, Peter B, Broderick, Stephen R, Jones, David R, Topalian, Suzanne L, Pardoll, Drew M, Brahmer, Julie R, Chaft, Jamie E, Forde, Patrick M
• Format: Journal Article
• Language: English
• Published: United States 16.02.2023
• Subjects: B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung - drug therapy; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - surgery; Neoadjuvant Therapy; Nivolumab - therapeutic use
• ISSN: 1557-3265
• DOI: 10.1158/1078-0432.CCR-22-2994

Neoadjuvant anti-PD-1 therapy has shown promise for resectable non-small cell lung cancer (NSCLC). We reported the first phase I/II trial of neoadjuvant nivolumab in resectable NSCLC, finding it to be safe and feasible with encouraging major pathological responses (MPR). We now present 5-year clinical outcomes from this trial, representing to our knowledge, the longest follow-up data for neoadjuvant anti-PD-1 in any cancer type. Two doses of nivolumab (3 mg/kg) were administered for 4 weeks before surgery to 21 patients with Stage I-IIIA NSCLC. 5-year recurrence-free survival (RFS), overall survival (OS), and associations with MPR and PD-L1, were evaluated. With a median follow-up of 63 months, 5-year RFS and OS rates were 60% and 80%, respectively. The presence of MPR and pre-treatment tumor PD-L1 positivity (TPS ≥1%) each trended toward favorable RFS; HR, 0.61 [95% confidence interval (CI), 0.15-2.44] and HR, 0.36 (95% CI, 0.07-1.85), respectively. At 5-year follow-up, 8 of 9 (89%) patients with MPR were alive and disease-free. There were no cancer-related deaths among patients with MPR. In contrast, 6/11 patients without MPR experienced tumor relapse, and 3 died. Five-year clinical outcomes for neoadjuvant nivolumab in resectable NSCLC compare favorably with historical outcomes. MPR and PD-L1 positivity trended toward improved RFS, though definitive conclusions are limited by cohort size.