# Preoperative Immune-Related Adverse Events in Resectable NSCLC Treated With Neoadjuvant Nivolumab Plus Chemotherapy: A Multicenter Retrospective Analysis

## TL;DR

About 20% of lung cancer patients experienced immune-related side effects before surgery when treated with nivolumab and chemotherapy, which affected treatment completion and surgery scheduling.

## Contribution

This study is the first to characterize preoperative immune-related adverse events in neoadjuvant chemoimmunotherapy for resectable NSCLC.

## Key findings

- Preoperative irAEs occurred in 18.5% of patients and were linked to lower treatment completion and higher surgery cancellation rates.
- Tumor size over 3.8 cm and eosinophil fraction ≥2.0% were identified as potential predictors of preoperative irAEs.
- Despite irAEs, most patients still underwent successful surgery with acceptable outcomes.

## Abstract

Preoperative immune-related adverse events (irAEs) during neoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer (NSCLC) remain poorly characterized. We aimed to evaluate their frequency, clinical impact, and associated risk factors.

This prespecified subanalysis of the multicenter CReGYT-04 Neo-Venus study retrospectively examined 130 patients with resectable NSCLC (stage IIA-IIIB, Union for International Cancer Control, eighth edition) treated with neoadjuvant nivolumab plus platinum-doublet chemotherapy. Clinical data were collected from 29 Japanese institutions. Patients were stratified according to the presence or absence of preoperative irAEs. Exploratory logistic regression was used to identify predictive factors.

Preoperative irAEs were observed in 18.5% of the patients (n = 24). Patients with irAEs had a significantly lower neoadjuvant therapy completion rate (58.3% versus 92.5%, p <0.001) and a higher incidence of cancelled surgery (21.7% versus 5.8%, p = 0.029) than those without irAEs. There were 18 patients (78.3%) with irAEs who underwent surgical resection. R0 resection was achieved in 94.4%. The postoperative complication rates and length of hospital stay were comparable between the groups. The major pathologic response rate (38.9% versus 63.1%) and pathologic complete response rate (27.8% versus 36.8%) were lower in patients with preoperative irAEs. Tumor size greater than 3.8 cm and eosinophil fraction greater than or equal to 2.0% were identified as exploratory predictors of preoperative irAEs.

Preoperative irAEs occurred in approximately 20% of patients with resectable NSCLC treated with neoadjuvant nivolumab plus chemotherapy and were associated with treatment discontinuation and cancellation of surgery. Nevertheless, curative-intent surgery remained feasible and achieved acceptable perioperative outcomes in most patients with preoperative irAEs.