Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer.
Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer.
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曲妥珠单抗Deruxtecan治疗her2突变型非小细胞肺癌
DOI：
10.1056/nejmoa2112431
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发表时间：
2022-01-20
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人表皮生长因子受体 2 (HER2) 靶向疗法尚未获批用于非小细胞肺癌 (NSCLC) 患者。曲妥珠单抗 deruxtecan（以前称为 DS-8201）（一种 HER2 抗体药物偶联物）在 HER2 突变 NSCLC 患者中的疗效和安全性尚未得到广泛研究。我们进行了一项多中心、国际、2 期研究，其中对标准治疗难治的转移性 HER2 突变 NSCLC 患者给予曲妥珠单抗 deruxtecan（6.4 毫克/公斤体重）。主要结果是通过独立中央审查评估的客观反应。次要结局包括缓解持续时间、无进展生存期、总生存期和安全性。评估了 HER2 改变的生物标志物。共有 91 名患者入组。中位随访时间为 13.1 个月（范围：0.7 至 29.1）。 55% 的患者出现集中确认的客观缓解（95% 置信区间 [CI]，44 至 65）。中位缓解持续时间为 9.3 个月（95% CI，5.7 至 14.7）。中位无进展生存期为 8.2 个月（95% CI，6.0 至 11.9），中位总生存期为 17.8 个月（95% CI，13.8 至 22.1）。安全性与之前的研究基本一致； 46% 的患者发生 3 级或以上药物相关不良事件，最常见的事件是中性粒细胞减少症（19%）。 26% 的患者出现药物相关间质性肺疾病，并导致 2 名患者死亡。在不同 HER2 突变亚型以及未检测到 HER2 表达或 HER2 扩增的患者中观察到了反应。 Trastuzumab deruxtecan 在既往接受过治疗的 HER2 突变 NSCLC 患者中显示出持久的抗癌活性。安全性包括间质性肺疾病，其中两例是致命的。观察到的毒性作用与之前报道的研究基本一致。 （由第一三共和阿斯利康资助；DESTINY-Lung01 ClinicalTrials.gov 编号，NCT03505710。）
Human epidermal growth factor receptor 2 (HER2)–targeted therapies have not been approved for patients with non–small-cell lung cancer (NSCLC). The efficacy and safety of trastuzumab deruxtecan (formerly DS-8201), a HER2 antibody–drug conjugate, in patients with HER2-mutant NSCLC have not been investigated extensively. We conducted a multicenter, international, phase 2 study in which trastuzumab deruxtecan (6.4 mg per kilogram of body weight) was administered to patients who had metastatic HER2-mutant NSCLC that was refractory to standard treatment. The primary outcome was objective response as assessed by independent central review. Secondary outcomes included the duration of response, progression-free survival, overall survival, and safety. Biomarkers of HER2 alterations were assessed. A total of 91 patients were enrolled. The median duration of follow-up was 13.1 months (range, 0.7 to 29.1). Centrally confirmed objective response occurred in 55% of the patients (95% confidence interval [CI], 44 to 65). The median duration of response was 9.3 months (95% CI, 5.7 to 14.7). Median progression-free survival was 8.2 months (95% CI, 6.0 to 11.9), and median overall survival was 17.8 months (95% CI, 13.8 to 22.1). The safety profile was generally consistent with those from previous studies; grade 3 or higher drug-related adverse events occurred in 46% of patients, the most common event being neutropenia (in 19%). Adjudicated drug-related interstitial lung disease occurred in 26% of patients and resulted in death in 2 patients. Responses were observed across different HER2 mutation subtypes, as well as in patients with no detectable HER2 expression or HER2 amplification. Trastuzumab deruxtecan showed durable anticancer activity in patients with previously treated HER2-mutant NSCLC. The safety profile included interstitial lung disease that was fatal in two cases. Observed toxic effects were generally consistent with those in previously reported studies. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Lung01 ClinicalTrials.gov number, NCT03505710.)