Neoadjuvant therapy for NSCLC: From monotherapy to precision combination therapy.

Abstract

Neoadjuvant therapy aims to reduce tumor size, increase resectability, eliminate micrometastases, and improve outcomes for patients with advanced non‑small cell lung cancer (NSCLC). Platinum‑based chemotherapy was the standard neoadjuvant treatment strategy in the past. In recent years, the emergence of targeted therapy and immunotherapy has significantly promoted neoadjuvant strategies. Immune checkpoint inhibitors (ICIs) such as programmed cell death 1 (PD-1) inhibitors, programmed cell death ligand 1 (PD-L1) inhibitors, and cytotoxic T lymphocyte associated protein 4 (CTLA-4) inhibitors represent established therapeutic agents in the treatment of NSCLC. In terms of targeted therapy, tyrosine kinase inhibitors (TKI) against driver genes such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) have shown promising potential in patients with driver mutations. Meanwhile, numerous clinical studies have demonstrated that neoadjuvant combination therapy can markedly improve pathological complete response (pCR) rates and event‑free survival (EFS). The CheckMate-816 trial confirmed that nivolumab plus chemotherapy outperforms chemotherapy alone. However, there are still several challenges. Drug resistance, the gap between pathological response and long-term survival benefit, and the limited predictive accuracy of current biomarkers remain major challenges in neoadjuvant therapy. In the future, efforts should focus on the search for precise predictive tools to develop personalized treatment strategies. Validation of neoadjuvant combination regimens aimed at enhancing clinical efficacy and quality of life for NSCLC patients is ongoing. This review summarizes the current advances and future directions of neoadjuvant therapy for NSCLC.