• Jingying Nong, Yanfei Gu, Shuyang Yao, and Yi Zhang.
• Department of Thoracic Surgery, Xuanwu Hospital, Cancer Center of National Clinical Research Center for Geriatric Diseases, Diagnostic and Treatment Center of Lung Cancer, Capital Medical University, Beijing, China.
• Medicine (Baltimore). 2021 Jul 23; 100 (29): e26650.

RationalEpidermal 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, clinically obtainable management for this subset of patients remains an unmet need. there are no previous reports of upfront combination therapy with immunotherapy and chemotherapy for lung adenocarcinoma with brain metastasis harboring EGFR 20 insertion.Patient ConcernsA 56-year-old man who sought care for dry cough was diagnosed with lung adenocarcinoma with brain metastases indicating a poor prognosis.DiagnosisNext-generation sequencing of lung biopsied tissue revealed an EGFR exon 20 in-frame insertion (P772_H773insYNP+H773Y).InterventionsThe patient started treatment of pemetrexed and carboplatin plus programmed cell death-1 inhibitor sintilimab in November 2019.OutcomesThe patient achieved partial responses both intra- and extra-cranially. After 6 cycles of treatment, the patient accepted sintilimab plus pemetrexed every 3 weeks as maintenance therapy, which was well-tolerated without any toxicity and is still ongoing after 18 months since initiation of 1st-line treatment.LessonsThis is the first case report of the clinical benefit of upfront immune checkpoint inhibitors (ICIs) plus chemotherapy for a brain metastatic NSCLC patient harboring EGFR exon 20 insertion mutation. Further study is needed to validate the predictor involved in responders to ICIs-based therapy with EGFR mutations.Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.

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