Lung Adenocarcinoma Harboring EGFR Kinase Domain Duplication (EGFR-KDD) Confers Sensitivity to Osimertinib and Nivolumab: A Case Report

BACKGROUND: Kinase domain duplication of EGFR (EGFR-KDD) is a rare oncogenic driver alteration and serves as a potential therapeutic target. Its effect on EGFR–tyrosine kinase inhibitors (TKIs), especially the third-generation drug Osimertinib, and immune checkpoint inhibitors (ICIs) remains inconclusive. CASE PRESENTATION: A 45-year old male with lung adenocarcinoma progressed with liver metastasis after receiving pemetrexed and cisplatin as adjuvant chemotherapy. Targeted next-generation sequencing (NGS) identified an EGFR-KDD in the resected left upper lung. Icotinib was used in the following treatment and the liver metastasis was found to shrink but the progression-free survival (PFS) only lasted for 4 months with the appearance of right hepatic metastasis. Meantime, the same EGFR-KDD was identified in the left hepatic re-biopsy. Afterward, the patient benefited from the third-line therapy of Osimertinib with a PFS as long as 21 months. Then he progressed with enlarged mediastinal lymph nodes, and targeted NGS consistently identified EGFR-KDD, as well as a new RELN p.G1774E mutation. Given the continually increasing tumor mutation burden (TMB, 3.4 mutation/Mb) and PD-L1 expression-based tumor proportion score (TPS, 1%), Nivolumab was used as the fourth-line salvage therapy, which lead to considerable efficacy, with decreased blood carcinoembryonic antigen (CEA), regressed mediastinal lymph nodes, and reduced liver metastases. CONCLUSIONS: Our case provided direct evidence to support the role of Osimertinib in the treatment of EGFR-KDD, as well as added valuable insights into application of immune-based therapeutics in the specific subgroups bearing EGFR alteration(s).