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

Samuel Rosner, Joshua E Reuss, Marianna Zahurak, Jiajia Zhang, Zhen Zeng, Janis Taube, Valsamo Anagnostou, Kellie N Smith, Joanne Riemer, Peter B Illei, Stephen R Broderick, David R Jones, Suzanne L Topalian, Drew M Pardoll, Julie R Brahmer, Jamie E Chaft, Patrick M Forde, Samuel Rosner, Joshua E Reuss, Marianna Zahurak, Jiajia Zhang, Zhen Zeng, Janis Taube, Valsamo Anagnostou, Kellie N Smith, Joanne Riemer, Peter B Illei, Stephen R Broderick, David R Jones, Suzanne L Topalian, Drew M Pardoll, Julie R Brahmer, Jamie E Chaft, Patrick M Forde

Abstract

Purpose: 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.

Patients and methods: 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.

Results: 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.

Conclusions: 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.

©2023 The Authors; Published by the American Association for Cancer Research.

Figures

Figure 1.
Figure 1.
A–D, Kaplan–Meier curves depicting the recurrence-free survival (A) and overall survival (B) for patients who underwent definitive resection after receiving neoadjuvant nivolumab. C, Depicts the recurrence-free survival for patients with or without major pathological response after neoadjuvant nivolumab. D, Shows the recurrence-free survival stratified by pre-treatment tumor PD-L1 expression. The dashed lines represent the 95% confidence intervals for each KM-curve. Abbreviations: Major pathological response, MPR; Programmed death-ligand 1, PD-L1; Hazard ratio, HR; Confidence Interval, CI.
Figure 2.
Figure 2.
Swimmer plot summarizing follow-up and recurrence patterns for patients with or without a major pathological response after neoadjuvant nivolumab. Follow-up is limited to 60 months. Abbreviation: Pathological complete response, pCR.

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Source: PubMed

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