Simultaneous occurrence of HER2 mutation and PD-L1 high expression in EGFR-mutant NSCLC: a case report

Abstract

In non-small cell lung cancer (NSCLC), EGFR and HER2 mutations are generally considered mutually exclusive events, with a co-occurrence probability estimated to be less than 1%. Patients with either EGFR or HER2 mutations tend to exhibit low PD-L1 expression levels. The simultaneous presence of both EGFR and HER2 mutations accompanied by high PD-L1 expression is exceedingly rare. This study reports a female patient who was admitted to the hospital after a routine physical examination revealed a right lung nodule and was diagnosed with “right lung adenocarcinoma (cT2aN2aM1c1, IVA; EGFR 21 L858R mutation; HER2 exon 8 mutation; PD-L1 TPS 60%).” The patient was immediately started on first-line third-generation EGFR-targeted therapy (Furmonertinib), but disease progression occurred after just 4.4 months (malignant pleural effusion and pericardial effusion). As the patient refused repeat biopsy, treatment with an ADC drug (Trastuzumab rezetecan) was initiated. Disease control was achieved after only one cycle of treatment, and the regimen was continued thereafter. The progression-free survival has exceeded 5.3 months, and at the time of writing this report, the disease remained well-controlled. This paper presents the first report of this rare and therapeutically challenging combination of molecular pathological features—concurrent EGFR and HER2 mutations with high PD-L1 expression in an NSCLC patient. When standard first-line third-generation EGFR-TKIs proved ineffective, the successful use of an anti-HER2 ADC drug to control the tumor demonstrates its potential clinical value. However, whether all patients initially presenting with this pathological molecular subtype will achieve consistent efficacy remains to be further investigated.