人类表皮生长因子受体2 (HER2)靶向疗法尚未被批准用于非小细胞肺癌(NSCLC)患者。曲妥珠单抗德鲁替康(原DS-8201)是一种HER2抗体-药物偶联物，在HER2突变型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，其中曲妥珠单抗德鲁替康(6.4mg/kg体重)用于标准治疗难治的转移性HER2突变型NSCLC患者。主要结果是通过独立中心审查评估的客观反应。次要结果包括反应持续时间、无进展生存期、总生存期和安全性。评估HER2改变的生物标志物。

共有91名患者入选。中位随访时间为13.1个月(范围0.7至29.1)。55%的患者出现了中央证实的客观缓解(95%可信区间[CI]， 44 ~ 65)。中位缓解时间为9.3个月(95% CI 5.7 ~ 14.7)。中位无进展生存期为8.2个月(95% CI, 6.0 - 11.9)，中位总生存期为17.8个月(95% CI, 13.8 - 22.1)。安全性概况与以前的研究基本一致;46%的患者发生了3级或更高级别的药物相关不良事件，最常见的是中性粒细胞减少症(19%)。26%的患者发生与药物相关的间质性肺疾病，2例患者死亡。在不同的HER2突变亚型中，以及在没有检测到HER2表达或HER2扩增的患者中观察到应答。

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. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Lung01 ClinicalTrials.gov number, NCT03505710.).

原文链接

pubmed.ncbi.nlm.nih.gov/34534430/

百度浏览   来源 : 医微客   

版权声明：本网站所有注明来源“医微客”的文字、图片和音视频资料，版权均属于医微客所有，非经授权，任何媒体、网站或个人不得转载，授权转载时须注明来源：”医微客”。本网所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，转载仅作观点分享，版权归原作者所有。不希望被转载的媒体或个人可与我们联系，我们将立即进行删除处理。 本站拥有对此声明的最终解释权。