Case Report: Exceptional survival with immunotherapy in a patient with EGFR exon 20 insertion (p.S768_D770dup) and high PD-L1 expression

EGFR exon 20 insertion (ex20ins) NSCLC typically shows limited response to immunotherapy. We report a rare case of a smoker with metastatic EGFR ex20ins (p.S768_D770dup) and high PD-L1 expression (TPS 50%) who achieved exceptional survival (OS = 63 months). Following progression on chemotherapy and intolerance to afatinib, the patient received paclitaxel plus tislelizumab. This combination yielded durable disease control. While the overall benefit of immune checkpoint inhibitors (ICIs) in EGFR-mutant NSCLC remains limited, this case suggests that chemo-immunotherapy (particularly taxane + PD-1 inhibition) may provide significant benefit in ex20ins tumors with high PD-L1 expression and smoking history. These findings highlight the critical value of targeted molecular profiling and offer a viable precision oncology strategy when novel targeted agents are inaccessible.