Durable response to immunotherapy plus chemotherapy in a patient with untreated, brain-metastatic, EGFR exon 20 insertion mutation lung adenocarcinoma: A case report

Epidermal growth factor receptor (EGFR) 20 exon insertion is the second most common EGFR aberrations in non-small cell lung cancer (NSCLC). Despite some novel EGFR inhibitors showing encouraging antitumor activity, clinically obtainable management for this subset of patients remains an unmet need. Although immune checkpoint inhibitors (ICIs) have led to unprecedented clinical benefit in metastatic NSCLC, clinical evidence suggests that EGFR mutant lung cancers rarely derive benefit from treatment with ICIs. We report that a lung adenocarcinoma patient harboring an actionable gene mutation of EGFR exon 20 insertion, high PD-L1 expression, high tumor mutational burden, as well as alterations in immune-related genes including CTNNB1 (Catenin β1) S37F and ARID2 (AT-rich interactive domain-containing protein 2) E1056X responded to upfront PD-1 inhibitor plus chemotherapy. As an advanced-stage lung cancer with brain metastases indicating poor prognosis, the patient achieved an unusual and durable response over 15 months. Upfront ICIs plus chemotherapy might be an option for some NSCLC patients harboring EGFR exon 20 insertion mutation. Further study is needed to validate the predictor involved in responders to ICIs-based therapy with EGFR mutations.