Advances in immunotherapy for driver gene-positive non-small cell lung cancer: a narrative review

Although immunotherapy has become the standard treatment for driver gene-negative advanced non-small cell lung cancer (NSCLC), its efficacy in driver gene-positive NSCLC patients remains conversational. This narrative review systematically and critically analyzes recently published literature, aiming to improve the current landscape of immunotherapy for driver gene-positive NSCLC.

The databases of PubMed, Web of Science, Scopus, and Google Scholar were searched for relevant articles, including those published in leading journals and conference proceedings. Search queries were constructed using keywords ("immunotherapy", "non-small cell lung cancer", "driver gene-positive") and their combinations. Literature was included via dual independent screening and team meetings, followed by comprehensive interpretation, resulting in a high-quality literature corpus focused on advances in immunotherapy for driver gene-positive NSCLC.

This article reviews the recent advances and challenges in immunotherapy for driver gene-positive NSCLC, focusing on common driver gene mutations. Significant variations exist in how different driver genes regulate the tumor immune microenvironment, leading to disparate immunotherapy response rates. While targeted therapy is the first-line treatment for NSCLC with epidermal growth factor receptor (EGFR) mutations, immunotherapy combinations should be explored when drug resistance occurs. Immunotherapy plus chemotherapy is preferred in patients with Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated NSCLC, whereas antibody-drug conjugates plus immunotherapy may be more appropriate for NSCLC with human epidermal growth factor receptor 2 (HER2) alterations. Despite the accumulation of studies of patients with common alterations, studies of patients with uncommon alterations are still lacking. Neoadjuvant immunotherapy combined with chemotherapy is currently being explored for driver gene-positive NSCLC.

Many questions remain about the use of immunotherapy for the treatment of driver gene-positive NSCLC. With optimized biomarker and combination therapies, individualized strategies may be further developed for overcoming drug resistance.