Immunotherapy-based combination strategies for treatment of EGFR-TKI-resistant NSCLC

The rapid development of molecular targeted therapy brings hope to patients with advanced non-small-cell lung cancer (NSCLC). However, drug resistance inevitably occurs during treatment with EGFR-tyrosine kinase inhibitors (TKIs). Osimertinib, a third-generation EGFR-TKI, shows a favorable prognosis in T790M-positive NSCLC. Unfortunately, acquired resistance is still a challenge for both patients and clinicians. There is still no consensus on the optimal treatment. PD-1 and its ligand receptor 1 (PD-L1) inhibitors have yielded great progress, especially in patients with no actionable mutations. In this review, the authors take stock of the relationship between EGFR mutations and PD-L1 expression and summarize the important clinical studies on immunotherapy-inhibitor-based treatment in patients with EGFR-TKI-resistant NSCLC. Plain language summary Lung cancer is one of the most common malignant cancers worldwide. Specific genes are known to drive cancer growth in advanced non-small-cell lung cancer (NSCLC) and targeted therapies against these genes and their proteins have significantly improved survival. However, resistance to these therapies inevitably occurs and there is still no consensus on the best treatment strategy after resistance develops. Several related articles have discussed the relationship between treatment resistance and the production of PD-L1 proteins in cancer cells (which helps them avoid the body's immune system). EGFR-tyrosine kinase inhibitors (TKIs), a type of targeted therapy, were also reported to influence the production of PD-L1. Therefore, the authors hypothesize that immunotherapy (a type of targeted therapy that forces the body's immune system to attack cancers regardless of PD-L1 production) may be a new option for treatment-resistant patients. In this review, the feasibility of EGFR-TKIs in combination with immunotherapy is clarified.