Immune checkpoint inhibitors in driver mutation-positive nonsmall cell lung cancer: is there a role?

Despite advances in immunotherapy for nonsmall cell lung cancer patients, the clinical efficacy of drugs for patients with oncogenic driver mutations remains limited. This article aimed to comprehensively review the currently available data on the efficacy and safety of immune checkpoint blockade (ICB) for patients with driver mutation-positive lung cancer.

Despite the positive interaction between activation of oncogenic pathways and upregulated PD-L1 expression demonstrated in preclinical studies, the efficacy of single-agent ICB in patients with oncogenic mutation has largely been discouraging, except for those with KRAS mutations. The combination therapies using ICB with tyrosine kinase inhibitors (TKIs) for EGFR/ALK alteration raised a concern for the high incidence of treatment-related adverse events, notably hepatotoxicity and interstitial lung disease. A novel combination with bevacizumab demonstrated promising efficacy with tolerable safety profiles.

Other than patients with the KRAS mutation who demonstrate relatively favorable response to ICB, a single-agent ICB therapy should be considered for those who retain good performance status but have no other therapeutic options available. Further studies on the combination of ICB and TKI are needed to identify the most viable pair regarding safety. Additional studies using novel combination partners, such as anti-VEGF inhibitors, are also warranted.