Trastuzumab Deruxtecan in Patients With HER2 -Mutant Metastatic Non–Small-Cell Lung Cancer: Primary Results From the Randomized, Phase II DESTINY-Lung02 Trial

作者：Kōichi Goto, Yasushi Goto, Toshio Kubo, Kiichiro Ninomiya, Sang‐We Kim, David Planchard, Myung‐Ju Ahn, Egbert F. Smit, Adrianus J. de Langen, M. Pérol, Elvire Pons‐Tostivint, Silvia Novello, Hidetoshi Hayashi, Junichi Shimizu, Dong‐Wan Kim, Chih‐Hsi S. Kuo, James Chih‐Hsin Yang, Kaline Pereira, Fu-Chih Cheng, Ayumi Taguchi, Yingkai Cheng, Wenqin Feng, Zenta Tsuchihashi, Pasi A. Jänne · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.23.01361 · 被引用次数：323 · 研究领域：Lung Cancer Treatments and Mutations、HER2/EGFR in Cancer Research、Lung Cancer Research Studies

PURPOSE Trastuzumab deruxtecan (T-DXd) 5.4 and 6.4 mg/kg showed robust antitumor activity in multiple cancer indications; however, T-DXd 5.4 mg/kg has not been evaluated in patients with previously treated human epidermal growth factor receptor 2–mutant ( HER2m; defined as single-nucleotide variants and exon 20 insertions) metastatic non–small-cell lung cancer (mNSCLC). METHODS DESTINY-Lung02, a blinded, multicenter, phase II study, investigated T-DXd 5.4 mg/kg once every 3 weeks for the first time in previously treated (platinum-containing therapy) patients with HER2m mNSCLC and further assessed T-DXd 6.4 mg/kg once every 3 weeks in this population. The primary end point was confirmed objective response rate (ORR) per RECIST v1.1 by blinded independent central review. RESULTS One hundred fifty-two patients were randomly assigned 2:1 to T-DXd 5.4 or 6.4 mg/kg once every 3 weeks. As of December 23, 2022, the median duration of follow-up was 11.5 months (range, 1.1-20.6) with 5.4 mg/kg and 11.8 months (range, 0.6-21.0) with 6.4 mg/kg. Confirmed ORR was 49.0% (95% CI, 39.0 to 59.1) and 56.0% (95% CI, 41.3 to 70.0) and median duration of response was 16.8 months (95% CI, 6.4 to not estimable [NE]) and NE (95% CI, 8.3 to NE) with 5.4 and 6.4 mg/kg, respectively. Median treatment duration was 7.7 months (range, 0.7-20.8) with 5.4 mg/kg and 8.3 months (range, 0.7-20.3) with 6.4 mg/kg. Grade ≥ 3 drug-related treatment-emergent adverse events occurred in 39 of 101 (38.6%) and 29 of 50...