Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic Non-Small-Cell Lung Cancer: Primary Results From the Randomized, Phase II DESTINY-Lung02 Trial.
Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic Non-Small-Cell Lung Cancer: Primary Results From the Randomized, Phase II DESTINY-Lung02 Trial.
复制标题
HER2-突变转移性非小细胞肺癌患者的曲妥珠单抗Deruxtecan：随机，II期Destiny destiny-Lung02试验的主要结果。
DOI：
10.1200/jco.23.01361
复制
发表时间：
2023-11-01
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
曲妥珠单抗deruxtecan（T-DXd）5.4和6.4 mg/kg在多种癌症适应症中显示出稳健的抗肿瘤活性;然而，尚未在既往接受过治疗的人表皮生长因子受体2突变体（HER 2 m;定义为单核苷酸变体和外显子20插入）转移性非小细胞肺癌（mNSCLC）患者中评价T-DXd 5.4 mg/kg。DESTINY-Lung 02是一项设盲、多中心、II期研究，在既往接受过治疗（含铂治疗）的HER 2 m mNSCLC患者中首次研究了T-DXd 5.4 mg/kg每3周一次，并在该人群中进一步评估了T-DXd 6.4 mg/kg每3周一次。主要终点是盲态独立中心审查根据RECIST v1.1确认的客观缓解率（ORR）。152例患者以2：1的比例随机分配至T-DXd 5.4或6.4 mg/kg组，每3周一次。截至2022年12月23日，5.4 mg/kg组的中位随访持续时间为11.5个月（范围：1.1-20.6），6.4 mg/kg组为11.8个月（范围：0.6-21.0）。5.4和6.4 mg/kg剂量组确认的ORR分别为49.0%（95% CI，39.0 - 59.1）和56.0%（95% CI，41.3 - 70.0），中位缓解持续时间分别为16.8个月（95% CI，6.4至无法估计[NE]）和NE（95% CI，8.3至NE）。5.4 mg/kg组的中位治疗持续时间为7.7个月（范围，0.7-20.8），6.4 mg/kg组为8.3个月（范围，0.7-20.3）。5.4和6.4 mg/kg组分别有39/101例（38.6%）和29/50例（58.0%）患者发生≥ 3级药物相关治疗后出现的不良事件。5.4和6.4 mg/kg剂量组分别有13/101例（12.9%）和14/50例（28.0%）患者发生裁定的药物相关间质性肺病（每组中2.0% ≥ 3级）。T-DXd在两种剂量下均表现出具有临床意义的应答。安全性特征可接受且一般可管理，有利于T-DXd 5.4 mg/kg。
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). 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. 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 (58.0%) patients with 5.4 and 6.4 mg/kg, respectively. 13 of 101 (12.9%) and 14 of 50 (28.0%) patients had adjudicated drug-related interstitial lung disease (2.0% grade ≥ 3 in each arm) with 5.4 and 6.4 mg/kg, respectively. T-DXd demonstrated clinically meaningful responses at both doses. Safety profile was acceptable and generally manageable, favoring T-DXd 5.4 mg/kg.
DOI：
10.3390/curroncol30040330
发表时间：
2023-04-20
期刊：
Current oncology (Toronto, Ont.)
影响因子：
--
作者：
Verma S;Breadner D;Raphael J
通讯作者：
Raphael J