激素受体阳性 (HR+)、人表皮生长因子受体 2 (HER2) 低或 HER2 低或 HER2 低且曾接受内分泌治疗 (ET) 的转移性乳腺癌 (mBC) 患者 (pts) 中，曲妥珠单抗德鲁司康 (T-DXd) 与医生选择的化疗 (TPC) 的对比研究：DESTINY-Breas的初步研究结果

IF 2 3区工程技术 Q3 CHEMISTRY, MULTIDISCIPLINARY

Journal of Chemical & Engineering Data Pub Date : 2024-06-10 DOI:10.1200/jco.2024.42.17_suppl.lba1000

G. Curigliano, Xichun Hu, R. Dent, K. Yonemori, C. Barrios, J. O'Shaughnessy, Hans Wildiers, Qingyuan Zhang, Seock-Ah Im, C. Saura, L. Biganzoli, J. Sohn, C. Lévy, William Jacot, Natasha Begbie, Jun Ke, Gargi Surendra Patel, Aditya Bardia

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Pts had no prior CT for mBC, with ≥2 lines of ET for mBC, or 1 line of ET for mBC if PD occurred ≤24 months (mo) of adjuvant ET or ≤6 mo of ET+CDK4/6i for mBC. Primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) in HER2-low. Key secondary endpoints were PFS in intent-to-treat (ITT = HER2-low and -ultralow) and overall survival (OS). Other endpoints included objective response rate (ORR) and safety. Results: As of Mar 18, 2024, 866 pts (HER2-low, n=713; HER2-ultralow, n=153) were randomized; 90.4% had prior CDK4/6i. TPC group pts were selected for capecitabine (59.8%), nab-paclitaxel (24.4%) or paclitaxel (15.8%). T-DXd significantly improved PFS vs TPC in HER2-low (HR, 0.62 [95% CI 0.51, 0.74], P<0.0001; median, 13.2 vs 8.1 mo). ITT and HER2-ultralow results were consistent with HER2-low (Table). Median treatment duration was 11.0 mo (T-DXd) vs 5.6 mo (TPC). 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引用次数: 0

摘要

LBA1000 背景：T-DXd获准用于化疗（CT）≥1线后的HER2低（IHC 1+或2+/ISH阴性）mBC。DB-06（NCT04494425）评估了T-DXd在HER2低或-ultralow（IHC 0，膜染色）、HR+ mBC患者中的应用情况，这些患者在接受基于内分泌的治疗后疾病进展（PD），且既往未接受过CT治疗。方法：将HER2低或超低、HR+ mBC患者按1:1随机分配至T-DXd 5.4 mg/kg或TPC。患者既往未因 mBC 接受过 CT 治疗，且 mBC 曾接受过≥2 次 ET 治疗，或 mBC 曾接受过 1 次 ET 治疗（如果 PD 发生在辅助 ET 24 个月以内或 mBC 曾接受 ET+CDK4/6i 治疗 6 个月以内）。主要终点是经盲法独立中央审查（BICR）确定的 HER2 低者的无进展生存期（PFS）。主要次要终点是意向治疗（ITT = HER2低和-ultralow）的无进展生存期（PFS）和总生存期（OS）。其他终点包括客观反应率（ORR）和安全性。研究结果截至2024年3月18日，866名患者（HER2-低，713人；HER2-超低，153人）接受了随机治疗；90.4%的患者曾接受过CDK4/6i治疗。TPC组患者被选中接受卡培他滨（59.8%）、纳布-紫杉醇（24.4%）或紫杉醇（15.8%）治疗。T-DXd与TPC相比，能明显改善HER2低者的PFS（HR，0.62 [95% CI 0.51, 0.74]，P<0.0001；中位13.2个月 vs 8.1个月）。ITT和HER2-ultralow结果与HER2-low一致（表）。中位治疗时间为 11.0 个月（T-DXd）vs 5.6 个月（TPC）。在第一次中期分析时，OS 尚不成熟（HER2-低HR，0.83 [95% CI 0.66, 1.05]，P=0.1181；中位随访 18.6 个月）。40.6%的患者（T-DXd）与31.4%的患者（TPC）发生了等级（Gr）≥3的药物相关不良事件。49例（11.3%；0.7%为3/4级，0.7%为5级）与1例（0.2%为2级）接受T-DXd治疗的患者与接受TPC治疗的患者相比，发生了裁定的间质性肺病/肺炎。结论T-DXd与TPC（CT）相比，在HER2低的mBC患者中，T-DXd的PFS获益具有统计学意义和临床意义。HER2-超低的结果与HER2-低的结果一致。安全性与已知情况一致。DB-06将T-DXd确立为HER2低、HR+ mBC患者≥1次内分泌治疗后的标准治疗方法。临床试验信息：NCT04494425 .[表格：见正文］

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Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): Primary results from DESTINY-Breas

LBA1000 Background: T-DXd is approved for HER2-low (IHC 1+ or 2+/ISH-negative) mBC after ≥1 line of chemotherapy (CT). DB-06 (NCT04494425) evaluated T-DXd in pts with HER2-low or -ultralow (IHC 0 with membrane staining), HR+ mBC after disease progression (PD) on endocrine-based therapy and no prior CT for mBC. Methods: Pts with HER2-low or -ultralow, HR+ mBC were randomized 1:1 to T-DXd 5.4 mg/kg or TPC. Pts had no prior CT for mBC, with ≥2 lines of ET for mBC, or 1 line of ET for mBC if PD occurred ≤24 months (mo) of adjuvant ET or ≤6 mo of ET+CDK4/6i for mBC. Primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) in HER2-low. Key secondary endpoints were PFS in intent-to-treat (ITT = HER2-low and -ultralow) and overall survival (OS). Other endpoints included objective response rate (ORR) and safety. Results: As of Mar 18, 2024, 866 pts (HER2-low, n=713; HER2-ultralow, n=153) were randomized; 90.4% had prior CDK4/6i. TPC group pts were selected for capecitabine (59.8%), nab-paclitaxel (24.4%) or paclitaxel (15.8%). T-DXd significantly improved PFS vs TPC in HER2-low (HR, 0.62 [95% CI 0.51, 0.74], P<0.0001; median, 13.2 vs 8.1 mo). ITT and HER2-ultralow results were consistent with HER2-low (Table). Median treatment duration was 11.0 mo (T-DXd) vs 5.6 mo (TPC). OS was immature at first interim analysis (HER2-low HR, 0.83 [95% CI 0.66, 1.05], P=0.1181; median follow up, 18.6 mo). Grade (Gr) ≥3 drug-related adverse events occurred in 40.6% (T-DXd) vs 31.4% (TPC). Adjudicated interstitial lung disease / pneumonitis occurred in 49 (11.3%; 0.7% Gr 3/4, 0.7% Gr 5) vs 1 (0.2% Gr 2) pts receiving T-DXd vs TPC. Conclusions: T-DXd showed a statistically significant and clinically meaningful PFS benefit vs TPC (CT) in HER2-low mBC. HER2-ultralow results were consistent with HER2-low. Safety was in line with known profiles. DB-06 establishes T-DXd as a standard of care following ≥1 endocrine-based therapy for pts with HER2-low and -ultralow, HR+ mBC. Clinical trial information: NCT04494425 .[Table: see text]

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来源期刊

Journal of Chemical & Engineering Data 工程技术-工程：化工

CiteScore

5.20

自引率

19.20%

发文量

324

审稿时长

2.2 months

期刊介绍： The Journal of Chemical & Engineering Data is a monthly journal devoted to the publication of data obtained from both experiment and computation, which are viewed as complementary. It is the only American Chemical Society journal primarily concerned with articles containing data on the phase behavior and the physical, thermodynamic, and transport properties of well-defined materials, including complex mixtures of known compositions. While environmental and biological samples are of interest, their compositions must be known and reproducible. As a result, adsorption on natural product materials does not generally fit within the scope of Journal of Chemical & Engineering Data.