美国纪念斯隆-凯特林癌症中心Bob T. Li团队研究了曲妥珠单抗-Deruxtecan治疗HER2突变型非小细胞肺癌的疗效。这一研究成果发表在2021年9月18日出版的《新英格兰医学杂志》上。

人表皮生长因子受体2（HER2）靶向疗法尚未被批准用于治疗非小细胞肺癌（NSCLC）患者。曲妥珠单抗-deruxtecan（原名DS-8201）是HER2抗体-药物结合物，其在HER2突变型NSCLC患者中的有效性和安全性尚未得到广泛研究。

研究组进行了一项多中心、国际性的2期临床研究，采用曲妥珠单抗-deruxtecan治疗标准治疗无效、转移性、HER2突变的NSCLC患者。主要结局为经独立中央审查评估的客观缓解。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。研究组还评估了HER2改变的生物标志物。

该研究共纳入91例患者。中位随访时间为13.1个月。55%的患者出现了中央确认的客观缓解。中位缓解持续时间为9.3个月。中位无进展生存期为8.2个月，中位总生存期为17.8个月。安全性概况与先前研究的结果基本一致；46%的患者发生3级及以上药物相关不良事件，最常见的事件是中性粒细胞减少（19%）。26%的患者发生与药物相关的间质性肺病，2例患者死亡。研究组在不同的HER2突变亚型中，以及在未检测到HER2表达或HER2扩增的患者中观察到缓解。

研究结果表明，曲妥珠单抗-deruxtecan在先前治疗无效的HER2突变NSCLC患者中显示出持久的抗癌活性。安全性分析包括两例致命的间质性肺疾病。观察到的毒性作用通常与先前报告的研究一致。

附：英文原文

Title: Trastuzumab Deruxtecan in HER2-Mutant Non–Small-Cell Lung Cancer | NEJM

Author: Bob T. Li, M.D., Ph.D., M.P.H.,, Egbert F. Smit, M.D., Ph.D.,, Yasushi Goto, M.D., Ph.D.,, Kazuhiko Nakagawa, M.D.,, Hibiki Udagawa, M.D.,, Julien Mazières, M.D.,, Misako Nagasaka, M.D., Ph.D.,, Lyudmila Bazhenova, M.D.,, Andreas N. Saltos, M.D.,, Enriqueta Felip, M.D., Ph.D.,, Jose M. Pacheco, M.D.,, Maurice Pérol, M.D.,, Luis Paz-Ares, M.D.,, Kapil Saxena, M.D.,, Ryota Shiga, B.Sc.,, Yingkai Cheng, M.D., Ph.D.,, Suddhasatta Acharyya, Ph.D.,, Patrik Vitazka, M.D., Ph.D.,, Javad Shahidi, M.D.,, David Planchard, M.D., Ph.D.,, and Pasi A. Jnne, M.D., Ph.D.

Issue&Volume: 2021-09-18

Abstract:

Background

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.

Methods

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.

Results

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.

Conclusions

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.

DOI: 10.1056/NEJMoa2112431

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2112431