Antibody-drug conjugate helps patients with metastatic non-small cell lung cancer live longer, 延缓疾病进展
Dato-DXd治疗, 一种新的Trop-2导向抗体-药物偶联物, was found to significantly improve progression-free survival in patients with metastatic non-small cell lung cancer, 这种改善主要是由非鳞状肿瘤患者推动的.
这些结果 TROPION-Lung01 III期临床试验, 哪项比较了二线多西紫杉醇的治疗标准, 一种化学疗法, 与Dato-DXd, 抗体药物偶联物, 治疗前转移性非小细胞肺癌患者, 在欧洲肿瘤医学学会2023年大会上由. 亚伦Lisberg, assistant professor of medicine and thoracic medical oncologist at the 皇冠hga025大学洛杉矶分校健康 Jonsson Comprehensive 癌症中心 and the David Geffen 医学院 at UCLA.
Lisberg and the team found that patients treated 与Dato-DXd experienced a 25% reduction in the risk of disease progression or death compared to patients treated with docetaxel.
“虽然疾病进展总体上有所减少, the data clearly indicates that this benefit was primarily driven by patients with non-squamous tumors,利斯伯格说.
Lisberg指出，超过75%的入组患者患有非鳞状肿瘤. 在这个群体中, 该疗法将疾病进展或死亡的风险降低了37%, while patients with squamous tumors did not appear to derive a therapeutic benefit from Dato-DXd on trial.
除了, a trend in favor of Dato-DXd was observed in the interim overall survival analysis. In those assessments of how long a patient will live after receiving a therapy for their cancer, the improvement was most pronounced in the non-squamous population with a reduction in the risk of death of 23% 与Dato-DXd.
The improvements in progression-free and overall survival observed in the Dato-DXd treated patients were accompanied by significant tumor shrinkage 与Dato-DXd (26.4%) vs多西紫杉醇(12%).8%)，这一差异在非鳞状肿瘤患者中更为明显(31.8%).2% vs 12.8%).
The overall safety profile of Dato-DXd was superior to docetaxel as fewer patients had high grade drug related toxicities 与Dato-DXd (25%) compared to docetaxel (41%). Dato-DXd的常见副作用包括轻度至中度口腔溃疡和恶心. There were also fewer severe side effects leading to dose reduction or treatment discontinuation in Dato-DXd treated patients compared to those treated with docetaxel.
“Dato-DXd is the first antibody-drug conjugate in metastatic non-small cell lung cancer to demonstrate a statistically significant improvement in progression-free survival over the standard of care chemotherapy drug docetaxel, while evidencing a more favorable safety profile due to its unique ability to selectively delivers a potent chemotherapy directly into tumor cells,利斯伯格说.
这些发现令人鼓舞, 指出Lisberg, since the current standard of care second-line chemotherapy docetaxel is associated with modest benefit and substantial toxicity and suggest that Dato-DXd has the potential to be new therapy for patients with previously treated non-squamous non-small cell lung cancer.
TROPION-LUNG01研究设计
研究ers on the global TROPION-LUNG01 trial compared the effectiveness and tolerability of Dato-DXd vs docetaxel by randomizing 604 patients to receive either Dato-DXd (299 patients) or docetaxel (305) patients. Patients both with and without genetic driver mutations such as EGFR were enrolled and must have received multiple therapies for metastatic non-small cell lung cancer prior to enrollment. No minimum level of TROP-2 expression on the tumor surface was required for enrollment, 因为尚未发现TROP-2的表达与Dato-DXd的有效性相关, 到目前为止.
皇冠hga025大学洛杉矶分校在Dato-DXd开发中的领导地位
UCLA’s thoracic medical oncology team has been at the forefront of Dato-DXd’s global development punctuated by Lisberg’s ESMO 2023 TROPION-LUNG01 Presidential Symposium. 血液学/肿瘤学临床研究单位提供了关键支持, 以及利斯伯格在皇冠hga025大学洛杉矶分校胸部肿瘤医学的同事. 爱德华·加隆博士. 乔纳森·戈德曼博士. 艾米·卡明斯, who identified the potential of Dato-DXd early on in development and prioritized Dato-DXd for their heavily pretreated non-small cell lung cancer patients. These patients had a paucity of effective treatment options at the time of Dato-DXd trial enrollment and their participation was essential to the success of the TROPION-LUNG01 study, 许多人的生活得到了长期的改善, 由于Dato-DXd. The TRIO-US network also made significant contributions to the TROPION-LUNG01 study under the direction of Lisberg.
皇冠hga025大学洛杉矶分校和TRIO-US网络在未来Dato-DXd肺癌试验的前沿
This antibody-drug conjugate is now being evaluated as potential first-line therapy for patients with newly diagnosed metastatic non-small cell lung cancer on the TROPION-LUNG07/08 studies (NCT05555732/NCT05215340)，这两个项目最近都在皇冠hga025大学洛杉矶分校遍布南皇冠hga025的诊所开设. 除了, TRIO-US网络正在参与TROPION-LUNG07试验, 就像TROPION-LUNG01一样. These trials hold the promise to improve clinical outcomes for patients with metastatic non-small cell lung cancer by providing Dato-DXd to an even larger number of patients with non-squamous tumors.
Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate being jointly developed by AstraZeneca and Daiichi Sankyo.
