Adjuvant Pembrolizumab in Patients with Stage IIIA/N2 Non-Small Cell Lung Cancer Completely Resected after Neoadjuvant Concurrent Chemoradiation: A Prospective, Open-Label, Single-Arm, Phase 2 Trial

• Published in: Cancer research and treatment 2024, 56(4), , pp.1084-1095
• Main Authors: Shin, Junghoon, Park, Sehhoon, Kim, Kyung Hwan, Shin, Eui-Cheol, Jung, Hyun Ae, Cho, Jong Ho, Sun, Jong-Mu, Lee, Se-Hoon, Choi, Yong Soo, Ahn, Jin Seok, Kim, Jhingook, Park, Keunchil, Shim, Young Mog, Kim, Hong Kwan, Noh, Jae Myoung, Ahn, Yong Chan, Pyo, Hongryull, Ahn, Myung-Ju
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents, Immunological - pharmacology; Antineoplastic Agents, Immunological - therapeutic use; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - therapy; Chemoradiotherapy - methods; Chemotherapy, Adjuvant - methods; Female; Humans; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Male; Middle Aged; Neoadjuvant Therapy - methods; Neoplasm Staging; Original; Prospective Studies; 의학일반
• ISSN: 1598-2998; 2005-9256; 2005-9256
• DOI: 10.4143/crt.2024.084

Optimal treatment for stage IIIA/N2 non-small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT). In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to 2 years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39+PD-1+CD8+ T cells using fold changes in the percentage of proliferating Ki-67+ cells from days 1 to 7 of cycle 1 (Ki-67D7/D1). Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), nine (26%), and four (12%) had a tumor proportion score of < 1%, 1%-50%, and ≥ 50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a 5-year DFS rate of 29%. The OS rate was 86% at 2 years and 76% at 5 years. Patients with tumor recurrence within 6 months had a significantly lower Ki-67D7/D1 among CD39+PD-1+CD8+ T cells than those without (p=0.036). No new safety signals were identified. Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.