DESTINY-Lung02研究的最终分析结果及患者报告结局——一项曲妥珠单抗德鲁昔单抗治疗HER2突变转移性非小细胞肺癌患者的剂量盲法、随机、2期研究

Final Analysis Results and Patient-Reported Outcomes From DESTINY-Lung02-A Dose-Blinded, Randomized, Phase 2 Study of Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic NSCLC.

作者信息

Jänne Pasi A, Goto Yasushi, Kubo Toshio, Ninomiya Kiichiro, Kim Sang-We, Planchard David, Ahn Myung-Ju, Smit Egbert, Johannes de Langen Adrianus, Pérol Maurice, Pons-Tostivint Elvire, Novello Silvia, Hayashi Hidetoshi, Shimizu Junichi, Kim Dong-Wan, Pereira Kaline, Cheng Fu-Chih, Taguchi Ayumi, Cheng Yingkai, Dunton Kyle, Ali Ahmed, Goto Koichi

机构信息

Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Department of Thoracic Oncology, National Cancer Central Hospital, Tokyo, Japan.

出版信息

J Thorac Oncol. 2025 Jul 30. doi: 10.1016/j.jtho.2025.07.129.

DOI:10.1016/j.jtho.2025.07.129

PMID:40749900

Abstract

INTRODUCTION

Trastuzumab deruxtecan (T-DXd) demonstrated strong and durable responses in patients with previously treated HER2 (ERBB2) mutant (HER2m) metastatic NSCLC (mNSCLC) in the DESTINY-Lung02 primary analysis (December 23, 2022, data cutoff). This final analysis evaluated T-DXd efficacy and safety after 8 additional months of follow-up, including clinically relevant subgroups and patient-reported outcomes.

METHODS

DESTINY-Lung02 was a randomized, dose-blinded, multicenter, phase 2 trial. Patients with previously treated HER2m mNSCLC were randomized 2:1 to receive T-DXd 5.4 or 6.4 mg/kg once every 3 weeks. Primary end point was confirmed objective response rate by blinded independent central review.

RESULTS

As of August 25, 2023, 102 and 50 patients had received T-DXd 5.4 or 6.4 mg/kg, respectively. Median follow-up (Q1-Q3) was 15.8 (8.2-20.7) months and 16.5 (9.4-20.8) months, respectively. Confirmed objective response rate (95% confidence interval) was 50.0% (51/102; 39.9%-60.1%) and 56.0% (28/50; 41.3%-70.0%), respectively. Safety profile was acceptable and generally manageable. Accordingly, median treatment duration (Q1-Q3) was 7.7 (3.7-14.4) months and 8.3 (2.8-13.1) months; drug-related grade 3 or higher treatment-emergent adverse events occurred in 39.6% (40/101) and 60.0% (30/50), with nausea most common (67.3% [68/101], 82.0% [41/50]). Adjudicated drug-related interstitial lung disease occurred in 14.9% (15/101) and 32.0% (16/50), mostly grade 1 or 2 with one grade 5 in each arm. Health-related quality of life was preserved for the duration of T-DXd treatment while sample size was sufficient for analysis, with no adverse effects on health-related quality of life observed at either dose.

CONCLUSIONS

T-DXd demonstrated strong and durable responses at both doses, with no clinically significant changes in toxicity. The approved 5.4-mg/kg dose demonstrated a more favorable benefit-risk profile, including lower adjudicated drug-related interstitial lung disease incidence.

GOV IDENTIFIER

NCT04644237.

摘要

引言

在DESTINY-Lung02的初步分析（2022年12月23日，数据截止）中，曲妥珠单抗德鲁替康（T-DXd）在先前接受过治疗的HER2（ERBB2）突变（HER2m）转移性非小细胞肺癌（mNSCLC）患者中显示出强烈且持久的反应。这项最终分析评估了在额外8个月的随访后T-DXd的疗效和安全性，包括临床相关亚组和患者报告的结局。

方法

DESTINY-Lung02是一项随机、剂量盲法、多中心、2期试验。先前接受过治疗的HER2m mNSCLC患者按2:1随机分组，每3周接受一次5.4或6.4 mg/kg的T-DXd治疗。主要终点是由盲法独立中央审查确认的客观缓解率。

结果

截至2023年8月25日，分别有102例和50例患者接受了5.4或6.4 mg/kg的T-DXd治疗。中位随访时间（第1四分位数-第3四分位数）分别为15.8（8.2-20.7）个月和16.5（9.4-20.8）个月。确认的客观缓解率（95%置信区间）分别为50.0%（51/102；39.9%-60.1%）和56.0%（28/50；41.3%-70.0%）。安全性可接受且总体可控。因此，中位治疗持续时间（第1四分位数-第3四分位数）分别为7.7（3.7-14.4）个月和8.3（2.8-13.1）个月；39.6%（40/101）和60.0%（30/50）发生了与药物相关的3级或更高等级的治疗中出现的不良事件，其中恶心最为常见（67.3%[68/101]，82.0%[41/50]）。经判定的与药物相关的间质性肺病发生率分别为14.9%（15/101）和32.0%（16/50），大多为1级或2级，每组各有1例5级。在T-DXd治疗期间，健康相关生活质量得以维持，同时样本量足以进行分析，两种剂量均未观察到对健康相关生活质量有不良影响。