Efficacy with Trastuzumab Deruxtecan for Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutation in a Patient with a Poor Performance Status: A Case Report

Yuki Kato,1 Yasuhiro Kato,1 Yuji Minegishi,1,2 Takahiro Suzuki,1 Shinji Nakamichi,1 Masaru Matsumoto,1 Akihiko Miyanaga,1 Rintaro Noro,1 Kaoru Kubota,1 Yasuhiro Terasaki,3 Masahiro Seike,1 Akihiko Gemma1 1Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; 2Department of Pulmonary Medicine, Mitsui Memorial Hospital, Tokyo, Japan; 3Department of Analytic Human Pathology, Nippon Medical School, Tokyo, JapanCorrespondence: Yasuhiro KatoDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Sendagi 1-1-5 Bunkyo-ku, Tokyo, 113-8603, JapanEmail y-kato@nms.ac.jpAbstract: Antibody–drug conjugate (ADC) was novel type of anticancer drugs. Trastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2) targeting ADC, can be a novel treatment option for HER2 alternation (mutation, expression, amplification) advanced-stage non-small-cell lung cancer (NSCLC) from DESTINY-Lung01 result. Herein, we report a successful treatment with T-DXd for NSCLC harboring HER2 exon 20 insertion mutation in a patient with poor performance status (PS). We presented a case of a 52-year-old heavily pretreated female patient diagnosed with lung adenocarcinoma (cT1bN3M0, stage IIIB). After fifth-line pretreatment of systemic chemotherapy, primary tumor recurrence, pleural effusion, and miliary lung metastases were observed. The patient presented with hypoxia requiring oxygen therapy via nasal cannula at a flow rate of 4 L per minute, cancer pain, and cachexia requiring opioid treatment. Her Eastern Cooperative Oncology Group PS score was assessed 3. Comprehensive genomic profiling revealed HER2 exon 20 insertion mutation. After treatment with T-DXd was approved by the ethical review committee of Nippon Medical School Hospital, treatment was started. The tumor size decreased significantly, and her PS score decreased from 3 to 1, with improvement of hypoxia, cancer pain, and cachexia. The patient is still receiving treatment, ...