Recent advances in therapeutic strategies for non-small cell lung cancer

Abstract

The development of targeted therapy with small-molecule tyrosine kinase inhibitors and immunotherapy with immune checkpoints inhibitors has ushered in the era of precision medicine in treating lung cancer, which remains the leading cause of cancer-related deaths worldwide. Both targeted therapy and immunotherapy have significantly improved the survival of patients with metastatic non-small-cell lung cancer (NSCLC). Additionally, recent groundbreaking studies have demonstrated their efficacy in both the perioperative setting and following concurrent chemoradiotherapy in early-stage NSCLC. Despite significant advancements in first-line treatment options, disease progression remains inevitable for most patients with advanced NSCLC, necessitating the exploration and optimization of subsequent therapeutic strategies. Emerging novel agents are expanding treatment options in the first-line setting and beyond. Recently, emerging bispecific antibodies have shown enhanced efficacy. For instance, amivantamab has been approved as a treatment for epidermal growth factor receptor (EGFR)-mutant NSCLC, including those with EGFR exon 20 insertion mutations. Additionally, antibody-drug conjugates (ADCs), including HER2-targeting trastuzumab deruxtecan, TROP2-targeting ADCs, HER3-targeting patritumab deruxtecan, and MET-targeting telisotuzumab vedotin, have demonstrated promising outcomes in several clinical trials. This review summarizes the recent advancements and challenges associated with the evolving NSCLC therapeutic landscape.

Keywords: Antibody–drug conjugates; Biomarkers; Bispecific antibodies; Immune checkpoint inhibitors; NSCLC; Non-small-cell lung cancer; Targeted therapy.

Fig. 1

Major categories of therapeutic treatments for NSCLC. A Targeted therapies inhibit oncogenic receptor tyrosine kinases and their downstream signaling pathways, thereby suppressing tumor survival signals. B Immune checkpoint inhibitors, such as those targeting PD-1/PD-L1, B7/CTLA-4, and related pathways, restore T-cell function by reversing exhaustion, enhancing cytotoxic activity, and modulating the tumor immune microenvironment. C Bispecific and bifunctional antibodies simultaneously target molecules such as EGFR and MET, PD-1 and VEGF, or PD-1 and TIM-3, thereby reducing ligand-receptor interactions, promoting receptor degradation, and inducing antibody-mediated cellular cytotoxicity. D Antibody–drug conjugates deliver precise chemotherapeutic agents via cancer-specific antigen-targeting antibodies, enabling a bystander effect to eliminate neighboring cancer cells

Fig. 2

Proposed therapeutic strategies for patients with common EGFR mutation. ADC, antibody–drug conjugate; CCRT, concurrent chemoradiotherapy; MET, mesenchymal-epithelial transition