一种或多种内分泌治疗后，ENHERTU®显示HR阳性、HER2低转移和HER2超低转移性癌症的中位无进展生存期为13.2个月-动脉网

ENHERTU ® Demonstrated a Median Progression-Free Survival of 13.2 Months in HR Positive, HER2 Low and HER2 Ultralow Metastatic Breast Cancer Following One or More Lines of Endocrine Therapy

businesswire 等信源发布 2024-06-02 18:00

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TOKYO & BASKING RIDGE, N.J.--(BUSINESS WIRE)--Detailed positive results from the DESTINY-Breast06 phase 3 trial showed that ENHERTU® (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to standard of care chemotherapy in patients with HR positive, HER2 low (IHC 1+ or IHC 2+/ISH-) metastatic breast cancer and the overall trial population (patients with HR positive, HER2 low and HER2 ultralow [defined as IHC 0 with membrane staining] expression) following one or more lines of endocrine therapy.

东京和新泽西州巴斯金岭（BUSINESS WIRE）--DESTINY-Breast06 3期试验的详细阳性结果显示，与HR阳性，HER2低（IHC 1+或IHC 2+/ISH-）转移性乳腺癌患者和总体试验人群（HR阳性，HER2低和HER2超低[定义为具有膜染色的IHC 0表达的患者）的标准治疗化疗相比，ENHERTU®（曲妥珠单抗-德鲁替康）在无进展生存期（PFS）方面表现出统计学显着和临床意义的改善。

Results will be presented today as a late-breaking oral presentation (LBA1000) at the 2024 American Society of Clinical Oncology (#ASCO24) Annual Meeting..

结果将于今天在2024年美国临床肿瘤学会（ASCO24）年会上以最新的口头报告（LBA1000）形式发布。。

ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

ENHERTU是由Daiichi Sankyo（TSE:4568）发现的一种专门设计的HER2定向DXd抗体-药物偶联物（ADC），由Daiichi Sankyo和AstraZeneca（LSE/STO/Nasdaq:AZN）联合开发和商业化。

In the primary endpoint analysis of patients with HR positive, HER2 low metastatic breast cancer, ENHERTU reduced the risk of disease progression or death by 38% versus chemotherapy (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.51-0.74; p<0.0001). Median PFS was 13.2 months in the ENHERTU arm compared to 8.1 months in the chemotherapy arm as assessed by blinded independent central review (BICR)..

在HR阳性，HER2低转移性乳腺癌患者的主要终点分析中，与化疗相比，ENHERTU将疾病进展或死亡风险降低了38%（危险比[HR]:0.62；95%置信区间[CI]:0.51-0.74；p＜0.0001）。根据盲法独立中央审查（BICR）评估，ENHERTU组的中位PFS为13.2个月，而化疗组为8.1个月。。

In the key secondary endpoint analysis of PFS by BICR in the overall trial population, ENHERTU achieved a similar 37% reduction in the risk of disease progression or death versus chemotherapy with a median PFS of 13.2 months in the ENHERTU arm versus 8.1 months with chemotherapy (HR: 0.63; 95% CI: 0.53-0.75; p<0.0001)..

在BICR对整个试验人群PFS的关键次要终点分析中，ENHERTU组与化疗组相比，疾病进展或死亡风险降低了37%，中位PFS为13.2个月，化疗组为8.1个月（HR:0.63；95%CI:0.53-0.75；p＜0.0001）。。

A prespecified exploratory analysis showed the clinically meaningful improvement in PFS was consistent between patients with HER2 low and HER2 ultralow expression. In patients with HER2 ultralow expression, ENHERTU showed a 22% reduction in the risk of disease progression or death compared to chemotherapy with a median PFS of 13.2 months with ENHERTU versus 8.3 months with chemotherapy (HR: 0.78; 95% CI: 0.50-1.21)..

预先指定的探索性分析显示，HER2低表达和HER2超低表达患者的PFS临床意义改善是一致的。在HER2超低表达的患者中，与化疗相比，ENHERTU显示疾病进展或死亡风险降低22%，ENHERTU的中位PFS为13.2个月，化疗为8.3个月（HR:0.78；95%CI:0.50-1.21）。。

In patients with HER2 low expression, confirmed objective response rate (ORR) was 56.5% in the ENHERTU arm with nine complete responses (CRs) and 194 partial responses (PRs) versus 32.2% in the chemotherapy arm with zero CRs and 114 PRs. In the overall trial population, confirmed ORR in the ENHERTU arm was 57.3% with 13 CRs and 237 PRs versus 31.2% in the chemotherapy arm with zero CRs and 134 PRs.

在HER2低表达的患者中，ENHERTU组的确诊客观缓解率（ORR）为56.5%，其中9个完全缓解（CR）和194个部分缓解（PR），而化疗组为32.2%，CRs为零，114个PR。在整个试验人群中，ENHERTU组确诊的ORR为57.3%，其中13例CRs和237例PR，而化疗组为31.2%，CRs为零，134例PR。

In patients with HER2 ultralow expression, the confirmed ORR in the ENHERTU arm was 61.8% with four CRs and 43 PRs versus 26.3% in the chemotherapy arm with zero CRs and 20 PRs..

在HER2超低表达的患者中，ENHERTU组确诊的ORR为61.8%，其中4个CRs和43个PR，而化疗组为26.3%，CRs为零和20个PR。。

“Endocrine therapies are widely used early in the treatment of HR positive metastatic breast cancer, but following one or more lines of treatment, patients often derive limited efficacy from further endocrine-based therapy,” said Giuseppe Curigliano, MD, PhD, Professor of Medical Oncology at the University of Milan and the Head of the Division of Early Drug Development at the European Institute of Oncology, IRCCS, Italy and Principal Investigator for the trial.

“内分泌治疗在HR阳性转移性乳腺癌的早期治疗中被广泛使用，但在一种或多种治疗方案后，患者通常从进一步的内分泌治疗中获得有限的疗效，”米兰大学医学肿瘤学教授、意大利IRCCS欧洲肿瘤研究所早期药物开发部门负责人兼试验首席研究员Giuseppe Curigliano博士说。

“With a median progression-free survival of more than a year, the results from DESTINY-Breast06 show that ENHERTU could become a new standard of care for patients with HER2 low and HER2 ultralow expressing tumors following endocrine therapy in the metastatic setting.”.

“DESTINY-Breast06的结果显示，中位无进展生存期超过一年，ENHERTU可能成为转移性内分泌治疗后HER2低表达和HER2超低表达肿瘤患者的新标准。”。

The safety profile of ENHERTU in DESTINY-Breast06 was consistent with previous breast cancer clinical trials with no new safety concerns identified. The most common grade 3 or higher treatment related treatment emergent adverse events (TEAEs) occurring in 5% or more of patients treated with ENHERTU were neutropenia (20.7%), leukopenia (6.9%) and anemia (5.8%).

ENHERTU在DESTINY-Breast06中的安全性与之前的乳腺癌临床试验一致，没有发现新的安全性问题。在接受ENHERTU治疗的患者中，5%或更多的患者发生的最常见的3级或更高级别治疗相关的治疗紧急不良事件（TEAE）是中性粒细胞减少症（20.7%），白细胞减少症（6.9%）和贫血（5.8%）。

Interstitial lung disease (ILD) or pneumonitis occurred in 11.3% of patients treated with ENHERTU. The majority of ILD or pneumonitis events were low grade (grade 1 [n=7; 1.6%] or grade 2 [n=36; 8.3%]). There were three grade 3 ILD events (0.7%), zero grade 4 events and three grade 5 events (0.7%) as determined by an independent adjudication committee..

用ENHERTU治疗的患者中有11.3%发生间质性肺病（ILD）或肺炎。大多数ILD或肺炎事件为低度（1级[n=7；1.6%]或2级[n=36；8.3%]）。独立裁决委员会确定有三个三级ILD事件（0.7%），零级四级事件和三个五级事件（0.7%）。。

“ENHERTU continues to deliver pioneering results for a HER2 directed medicine across many different types of cancer,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “These latest results from DESTINY-Breast06 demonstrate clinically meaningful results with ENHERTU even in tumors with very low levels of HER2 expression, suggesting that it may have an important role in treating a wide range of HER2 expressing metastatic breast cancer.”.

“ENHERTU继续在许多不同类型的癌症中为HER2指导的药物提供开创性的结果，”第一三共全球研发主管Ken Takeshita医学博士说。“DESTINY-Breast06的这些最新结果表明，即使在HER2表达水平非常低的肿瘤中，ENHERTU也具有临床意义，这表明它可能在治疗广泛表达HER2的转移性乳腺癌中发挥重要作用。”。

“DESTINY-Breast06 represents another potential paradigm shift in how we treat patients across the spectrum of HR positive metastatic breast cancer,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “The results reinforce the potential for ENHERTU to improve outcomes earlier in the treatment landscape and in a broader population of patients with HER2 expressing breast cancer who have never before been eligible for a HER2 directed therapy.”.

阿斯利康肿瘤学研发执行副总裁、MBBChir博士苏珊·加尔布雷斯（SusanGalbraith）说：“DESTINY-Breast06代表了我们在HR阳性转移性乳腺癌患者治疗方面的另一个潜在范式转变。“这些结果增强了ENHERTU在治疗领域早期改善预后的潜力，以及在更广泛的表达HER2的乳腺癌患者中，这些患者以前从未有资格接受HER2指导的治疗。”。

Patients in the DESTINY-Breast06 trial received a median of two prior lines of endocrine therapy in each treatment arm. In the overall trial population, 14.9% of patients (n=65) in the ENHERTU arm had received one prior line of endocrine therapy and 67.8% (n=295) had received two prior lines of endocrine therapy.

DESTINY-Breast06试验中的患者在每个治疗组中接受了前两行内分泌治疗的中位数。在整个试验人群中，ENHERTU组14.9%的患者（n=65）接受过一次内分泌治疗，67.8%（n=295）接受过两次内分泌治疗。

No patients in the trial had received prior chemotherapy treatment in the metastatic setting. Median duration of follow-up was 18.2 months. As of the data cut-off of March 18, 2024, a total of 119 patients (14.0%) remained on study treatment, with 89 (20.5%) receiving ENHERTU and 30 (7.2%) receiving chemotherapy..

试验中没有患者在转移性环境中接受过化疗。中位随访时间为18.2个月。截至2024年3月18日的数据截止日期，共有119名患者（14.0%）仍在接受研究治疗，其中89名（20.5%）接受ENHERTU治疗，30名（7.2%）接受化疗。。

Summary of DESTINY-Breast06 Primary Analysis Results

DESTINY-Breast06主要分析结果摘要

Efficacy Measure

功效测量

HER2 low (IHC 1+ and IHC 2+/ISH-)

HER2低（IHC 1+和IHC 2+/ISH-）

Overall trial population (HER2 low and HER2 ultralow)

总体试验人群（HER2低和HER2超低）

HER2 ultralow (defined as IHC 0 with membrane staining)i,ii

HER2超低（定义为具有膜染色的IHC 0）i，ii

ENHERTU

(n=359)

（n=359）

Chemotherapy

化疗

(n=354)

（n=354）

ENHERTU

(n=436)

（n=436）

Chemotherapy

化疗

(n=430)

（n=430）

ENHERTU

(n=76)

（n=76）

Chemotherapy

化疗

(n=76)

（n=76）

PFS

PFS公司

Median PFSiii (months)

PFSiii中位数（月）

(95% CI)

（95%置信区间）

13.2 months

13.2个月

8.1 months

8.1个月

13.2 months

13.2个月

8.1 months

8.1个月

13.2 months

13.2个月

8.3 months

8.3个月

HR (95% CI)

人力资源（95%置信区间）

0.62 (0.51-0.74)

0.63 (0.53-0.75)

0.78 (0.50-1.21)

p-value

p值

p<0.0001

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操作系统

12 month OS Rate (%)

12个月OS率（%）

(95% CI)

（95%置信区间）

87.6%

81.7%

87.0%

81.1%

84.0%

78.7%

HR (95% CI)

人力资源（95%置信区间）

0.83 (0.66-1.05)

0.81 (0.65-1.00)v

0.81（0.65-1.00）伏

0.75 (0.43-1.29)

p-value

p值

p=0.1181vi

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ORR

Confirmed ORRi,iii,vii (%) (n)

已确认ORR，iii，vii（%）（n）

56.5% (203)

32.2% (114)

57.3% (250)

31.2% (134)

61.8% (47)

26.3% (20)

Best Overall Response

最佳总体响应

CR % (n)

铬%（n）

2.5% (9)

3.0% (13)

5.3% (4)

PR % (n)

PR%（n）

54.0% (194)

32.2% (114)

54.4% (237)

31.2% (134)

56.6% (43)

26.3% (20)

SD % (n)

标准偏差%（n）

34.8% (125)

48.0% (170)

33.9% (148)

49.3% (212)

28.9% (22)

55.3% (42)

Median DOR (months)

DOR中位数（月）

14.1 months

14.1个月

8.6 months

8.6个月

14.3 months

14.3个月

8.6 months

8.6个月

14.3 months

14.3个月

14.1 months

14.1个月

CI, confidence interval; CR, complete response; DOR, duration of response; HR, hazard ratio; NA, not available; PFS, progression-free survival; ORR, objective response rate; OS, overall survival; PR, partial response; SD, stable disease

CI，置信区间；CR，完全响应；DOR，响应持续时间；HR，风险比；NA，不可用；PFS，无进展生存期；ORR，客观回应率；OS，总体生存；PR，部分回应；SD，稳定疾病

i Descriptive analysis

一、描述性分析

ii Per central lab

ii每个中央实验室

iii As assessed by BICR

iii由BICR评估

iv Less than 40% maturity for interim OS analysis (HER2 low)

iv中期操作系统分析的成熟度低于40%（HER2低）

v No test of significance was performed in line with the multiple testing procedure

v没有按照多重测试程序进行显着性测试

vi P-value of 0.0046 required for statistical significance at this OS interim analysis

在此OS中期分析中，统计显着性所需的vi P值为0.0046

vii ORR is (CR + PR)

（vii）ORR（CR+PR）

Additional ENHERTU Data at ASCO

ASCO的其他ENHERTU数据

DESTINY-Breast03 Updated Results

DESTINY-Breast03更新结果

Updated overall survival (OS) results from the DESTINY-Breast03 phase 3 trial also presented as a poster show ENHERTU continued to demonstrate a clinically meaningful survival improvement over trastuzumab emtansine (T-DM1) after more than three years of follow-up in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab.

DESTINY-Breast03 3期临床试验的最新总生存期（OS）结果也以海报形式显示，在接受过曲妥珠单抗治疗的HER2阳性不可切除和/或转移性乳腺癌患者超过三年的随访后，ENHERTU继续显示出比曲妥珠单抗emtansine（T-DM1）有临床意义的生存改善。

In the updated analysis of OS, the key secondary endpoint of median OS has been reached in both treatment arms. Median OS was 52.6 months (95% CI: 48.7-NE) in the ENHERTU arm compared to 42.7 months (95% CI: 35.4-NE) in the T-DM1 arm (HR: 0.73; 95% CI: 0.56-0.94)..

在最新的OS分析中，两个治疗组均达到了中位OS的关键次要终点。ENHERTU组的中位OS为52.6个月（95%CI:48.7-NE），而T-DM1组为42.7个月（95%CI:35.4-NE）（HR:0.73；95%CI:0.56-0.94）。。

The safety profile of ENHERTU continues to be generally manageable and no cumulative toxicities were observed with longer follow-up. Grade 3 or higher treatment related TEAEs occurred in 48.6% of patients receiving ENHERTU. Since the prior data cut-off, there were four new ILD events (all grade 2).

ENHERTU的安全性仍然是可以控制的，并且在更长的随访时间内没有观察到累积毒性。接受ENHERTU治疗的患者中有48.6%发生3级或更高级别的治疗相关TEAE。自先前的数据截止以来，有四个新的ILD事件（均为2级）。

DESTINY-Breast07 Results

DESTINY-Breast07结果

Interim results from the DESTINY-Breast07 phase 1b/2 trial of ENHERTU alone or in combination with other anticancer therapies as a first-line treatment for HER2 positive metastatic breast cancer also were presented as an oral presentation. In the analysis, ENHERTU demonstrated promising activity as a monotherapy (n=75) and in combination with pertuzumab (n=50)..

DESTINY-Breast07 1b/2期ENHERTU单独或与其他抗癌疗法联合作为HER2阳性转移性乳腺癌的一线治疗的中期结果也以口服形式呈现。在分析中，ENHERTU作为单一疗法（n=75）和与帕妥珠单抗（n=50）联合使用显示出有希望的活性。。

Confirmed ORR in the ENHERTU monotherapy arm was 76.0% (80% CI: 68.5-82.4) with six CRs and 51 PRs. In the ENHERTU plus pertuzumab combination arm, confirmed ORR was 84.0% (80% CI: 75.3-90.5) with 10 CRs and 32 PRs. The 12-month PFS rate was 80.8% (80% CI: 73.7-86.1) in the ENHERTU monotherapy arm and 89.4% (80% CI: 81.9-93.9) in the ENHERTU plus pertuzumab combination arm..

ENHERTU单药治疗组确诊的ORR为76.0%（80%CI:68.5-82.4），其中6个CR和51个PR。在ENHERTU加pertuzumab联合治疗组中，确诊的ORR为84.0%（80%可信区间：75.3-90.5），其中10个CR和32个PR。ENHERTU单药治疗组12个月PFS率为80.8%（80%可信区间：73.7-86.1），ENHERTU联合帕妥珠单抗治疗组为89.4%（80%可信区间：81.9-93.9）。。

The safety of ENHERTU as a monotherapy and in combination with pertuzumab was consistent with known safety profiles of each therapy. Grade 3 or higher TEAEs occurred in 52.0% of patients in the ENHERTU monotherapy arm and 62.0% of patients in the ENHERTU plus pertuzumab combination arm. The most common grade 3 or higher TEAEs occurring in 5% or more of patients were neutropenia (27.0% in ENHERTU monotherapy arm; 24% in ENHERTU plus pertuzumab arm), anemia (4.0% in ENHERTU monotherapy arm; 14.0% in ENHERTU plus pertuzumab arm) and diarrhea (3.0% in ENHERTU monotherapy arm; 6.0% in ENHERTU plus pertuzumab arm).

ENHERTU作为单一疗法和与帕妥珠单抗联合使用的安全性与每种疗法的已知安全性一致。ENHERTU单药治疗组52.0%的患者发生3级或更高的TEAE，ENHERTU加培妥珠单抗联合治疗组62.0%的患者发生3级或更高的TEAE。5%或更多患者中最常见的3级或更高TEAE是中性粒细胞减少症（ENHERTU单药治疗组为27.0%；ENHERTU加pertuzumab组为24%），贫血（ENHERTU单药治疗组为4.0%；ENHERTU加pertuzumab组为14.0%）和腹泻（ENHERTU单药治疗组为3.0%；ENHERTU加pertuzumab组为6.0%）。

The majority of ILD or pneumonitis events were low grade (grade 1 or 2). In the ENHERTU monotherapy arm, there were two (2.7%) grade 1 events and five (6.7%) grade 2 events. There were no grade 3 or higher events observed in the ENHERTU monotherapy arm. In the ENHERTU plus pertuzumab combination arm, there were six (12.0%) grade 2 events and one (2.0%) grade 3 event.

大多数ILD或肺炎事件为低度（1级或2级）。在ENHERTU单药治疗组中，有两个（2.7%）1级事件和五个（6.7%）2级事件。在ENHERTU单药治疗组中没有观察到3级或更高的事件。在ENHERTU加pertuzumab联合治疗组中，有6例（12.0%）2级事件和1例（2.0%）3级事件。

There were no grade 4 or 5 events observed in the ENHERTU plus pertuzumab combination arm..

在ENHERTU加pertuzumab联合治疗组中没有观察到4级或5级事件。。

This is the first dataset of ENHERTU as a first-line treatment of HER2 positive metastatic breast cancer. Analyses from the ongoing DESTINY-Breast09 phase 3 trial will provide further insights regarding the efficacy and safety of ENHERTU in this HER2 positive patient population.

这是ENHERTU作为HER2阳性转移性乳腺癌一线治疗的第一个数据集。正在进行的DESTINY-Breast09 3期临床试验的分析将进一步了解ENHERTU在HER2阳性患者人群中的疗效和安全性。

About DESTINY-Breast06

关于DESTINY-Breast06

DESTINY-Breast06 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus investigator’s choice of chemotherapy (capecitabine, paclitaxel or nab paclitaxel) in patients with HR positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (defined as IHC 0 with membrane staining) advanced or metastatic breast cancer.

DESTINY-Breast06是一项全球性，随机，开放标签的3期临床试验，评估ENHERTU（5.4 mg/kg）与研究者选择的化疗（卡培他滨，紫杉醇或nab-紫杉醇）在HR阳性，HER2低（IHC 1+或IHC 2+/ISH-）或HER2超低（定义为IHC 0与膜染色）晚期或转移性乳腺癌患者中的疗效和安全性。

Patients in the trial had no prior chemotherapy for advanced or metastatic disease and received at least two lines of prior endocrine therapy in the metastatic setting. Patients also were eligible if they had received one prior line of endocrine therapy combined with a CDK4/6 inhibitor in the metastatic setting and experienced disease progression within six months of starting first-line treatment or received endocrine therapy as an adjuvant treatment and experienced disease recurrence within 24 months..

试验中的患者之前没有接受过晚期或转移性疾病的化疗，并且在转移性环境中接受了至少两行先前的内分泌治疗。如果患者在转移性环境中接受过一种先前的内分泌治疗联合CDK4/6抑制剂，并且在开始一线治疗的六个月内经历了疾病进展，或者接受了内分泌治疗作为辅助治疗，并且在24个月内经历了疾病复发，则患者也符合条件。。

The primary endpoint is PFS in the HR positive, HER2 low patient population as measured by BICR. Key secondary endpoints include PFS by BICR in the overall trial population (HER2 low and HER2 ultralow), OS in patients in the HER2 low patient population and OS in the overall trial population. Other secondary endpoints include ORR, DOR, time to first subsequent treatment or death, time to second subsequent treatment or death and safety.

主要终点是通过BICR测量的HR阳性，HER2低患者人群中的PFS。关键的次要终点包括BICR在总体试验人群中的PFS（HER2低和HER2超低），HER2低患者人群中患者的OS和总体试验人群中的OS。其他次要终点包括ORR，DOR，首次后续治疗或死亡的时间，第二次后续治疗或死亡的时间和安全性。

Analysis of the HER2 ultralow subgroup was not powered to demonstrate statistical significance..

HER2超低亚组的分析无法证明统计学意义。。

DESTINY-Breast06 enrolled 866 patients (n=713 for HER2 low and n=153 for HER2 ultralow) at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

DESTINY-Breast06在亚洲，欧洲，北美，大洋洲和南美洲的多个地点招募了866名患者（HER2-low n=713，HER2-ultralow n=153）。有关该试验的更多信息，请访问ClinicalTrials.gov。

About DESTINY-Breast03

关于DESTINY-Breast03

DESTINY-Breast03 is a global, head-to-head, randomized, open-label, pivotal phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus T-DM1 in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

DESTINY-Breast03是一项全球性，头对头，随机，开放标签，关键性的3期临床试验，评估ENHERTU（5.4 mg/kg）与T-DM1在HER2阳性不可切除和/或转移性乳腺癌患者中的疗效和安全性。之前用曲妥珠单抗和紫杉烷治疗。

The primary efficacy endpoint of DESTINY-Breast03 is PFS based on BICR. OS is the key secondary efficacy outcome measure. Other secondary endpoints include ORR, DOR, PFS based on investigator assessment and safety.

DESTINY-Breast03的主要疗效终点是基于BICR的PFS。OS是关键的次要疗效指标。其他次要终点包括基于研究者评估和安全性的ORR，DOR，PFS。

DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Oceania and South America. Primary results from DESTINY-Breast03 were published in The New England Journal of Medicine, with updated OS results published in The Lancet. For more information about the trial, visit ClinicalTrials.gov..

DESTINY-Breast03在亚洲，欧洲，北美，大洋洲和南美的多个地点招募了524名患者。DESTINY-Breast03的主要结果发表在《新英格兰医学杂志》上，最新的OS结果发表在《柳叶刀》上。有关该试验的更多信息，请访问ClinicalTrials.gov。。

About DESTINY-Breast07

关于DESTINY-Breast07

DESTINY-Breast07 is a global, randomized, open-label phase 1b/2 dose-finding and dose-expansion trial to explore the safety, tolerability and antitumor activity of ENHERTU alone or in combination with other anticancer agents in patients with HER2 positive metastatic breast cancer. The study consists of two phases: a dose escalation phase and a dose expansion phase.

DESTINY-Breast07是一项全球性，随机，开放标签的1b/2期剂量发现和剂量扩展试验，旨在探索ENHERTU单独或与其他抗癌药物联合用于HER2阳性转移性乳腺癌患者的安全性，耐受性和抗肿瘤活性。该研究包括两个阶段：剂量递增阶段和剂量扩展阶段。

The dose escalation phase enrolled patients with locally assessed HER2 positive or advanced metastatic breast cancer in second-line or later treatment. The dose expansion phase enrolled patients with locally assessed HER2 positive breast cancer previously untreated for advanced or metastatic disease..

剂量递增阶段招募了二线或后期治疗中局部评估为HER2阳性或晚期转移性乳腺癌的患者。剂量扩展阶段招募了先前未接受晚期或转移性疾病治疗的局部评估的HER2阳性乳腺癌患者。。

The primary endpoints of DESTINY-Breast07 are safety and tolerability. Secondary endpoints include ORR and PFS based on investigator assessment.

DESTINY-Breast07的主要终点是安全性和耐受性。次要终点包括基于研究者评估的ORR和PFS。

DESTINY-Breast07 enrolled 244 patients at multiple sites in Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov.

DESTINY-Breast07在亚洲，欧洲，北美和南美的多个地点招募了244名患者。有关该试验的更多信息，请访问ClinicalTrials.gov。

About Breast Cancer and HER2 Expression

关于乳腺癌和HER2表达

Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally.1 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis.2.

乳腺癌是世界上第二大常见癌症，也是全球癌症相关死亡的主要原因之一。1 2022年诊断出200多万例乳腺癌病例，全球死亡人数超过665000人。1虽然被诊断患有早期乳腺癌的患者的生存率很高，但只有约30%被诊断患有或进展为转移性疾病的患者预计在诊断后能活五年。

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including breast cancer.3 Patients with high levels of HER2 expression (IHC 3+ or IHC2+/ISH+) are classified as HER2 positive and treated with HER2 targeted therapies, representing approximately 15 to 20% percent of all breast cancers.4 Historically, tumors that were not classified as HER2 positive were classified as HER2 negative, despite the fact that many of these tumors still carry some level of HER2 expression.5 It is estimated that approximately 60% to 65% of HR positive breast cancers are HER2 low and potentially an additional 25% may be HER2 ultralow.6,7.

HER2是一种酪氨酸激酶受体生长促进蛋白，在包括乳腺癌在内的许多类型的肿瘤表面表达[3]。HER2表达水平高（IHC 3+或IHC2+/ISH+）的患者被归类为HER2阳性，并接受HER2靶向治疗，约占所有乳腺癌的15%至20%[4]。历史上，未被归类为HER2阳性的肿瘤被归类为HER2阴性，尽管事实上许多这些肿瘤仍然携带一定程度的HER2表达[5]。据估计，大约60%至65%的HR阳性乳腺癌HER2低，可能还有25%可能是HER2超低[6,7]。

Endocrine therapies are widely given consecutively in the early lines of treatment for HR positive metastatic breast cancer. However, following two lines of endocrine therapy, further efficacy with additional endocrine treatment is often limited. 8 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes.

内分泌治疗在HR阳性转移性乳腺癌的早期治疗中被广泛连续给予。然而，在两种内分泌治疗之后，额外内分泌治疗的进一步疗效通常是有限的。内分泌治疗后目前的护理标准是化疗，这与不良反应率和结果有关。

8,9,10,11.

Prior to the approval of ENHERTU following chemotherapy in HER2 low metastatic breast cancer based on the DESTINY-Breast04 trial, there were no targeted therapies approved specifically for patients with HER2 low expression.12 There are no targeted therapies specifically approved for patients with HER2 ultralow expression.13.

在基于DESTINY-Breast04试验的HER2低转移性乳腺癌化疗后批准ENHERTU之前，没有专门针对HER2低表达患者的靶向治疗.12没有专门针对HER2超低表达患者的靶向治疗.13。

About ENHERTU

关于ENHERTU

ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform.

ENHERTU（曲妥珠单抗deruxtecan；fam曲妥珠单抗deruxtecan nxki仅在美国）是HER2定向的ADC。ENHERTU采用第一三共专有的DXd ADC技术设计，是第一三共肿瘤学产品组合中的领先ADC，也是阿斯利康ADC科学平台中最先进的项目。

ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers..

ENHERTU由HER2单克隆抗体组成，该抗体通过基于四肽的可切割接头连接到许多拓扑异构酶I抑制剂有效载荷（exatecan衍生物DXd）。。

ENHERTU (5.4 mg/kg) is approved in more than 60 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+ or in-situ hybridization (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial..

ENHERTU（5.4 mg/kg）已在全球60多个国家获得批准，用于治疗不可切除或转移性HER2阳性（IHC 3+或原位杂交（ISH）+）乳腺癌的成年患者，这些患者先前曾接受过基于抗HER2的方案，无论是在转移性环境中还是在新辅助或辅助性环境中，并且根据DESTINY-Breast03试验的结果，在完成治疗后的六个月内或六个月内出现疾病复发。。

ENHERTU (5.4 mg/kg) is approved in more than 60 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ (ISH)-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial..

ENHERTU（5.4 mg/kg）已在全球60多个国家获得批准，用于治疗无法切除或转移性HER2低（IHC 1+或IHC 2+/（ISH）-）乳腺癌的成年患者，这些患者先前在转移性环境中接受过全身治疗，或根据DESTINY-Breast04试验的结果在完成辅助化疗后的六个月内或六个月内出现疾病复发。。

ENHERTU (5.4 mg/kg) is approved in more than 35 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial.

ENHERTU（5.4 mg/kg）已在全球35多个国家获得批准，用于治疗无法切除或转移性NSCLC的成年患者，这些患者的肿瘤具有激活的HER2（ERBB2）突变，这是通过当地或地区批准的测试检测到的，并且已经根据DESTINY-Lung02试验的结果接受了先前的全身治疗。

Continued approval in the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial..

美国对该适应症的持续批准可能取决于验证性试验中临床益处的验证和描述。。

ENHERTU (6.4 mg/kg) is approved in more than 45 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 and/or DESTINY-Gastric02 trials..

ENHERTU（6.4 mg/kg）已在全球45多个国家获得批准，用于治疗局部晚期或转移性HER2阳性（IHC 3+或IHC 2+/ISH+）胃或胃食管交界处（GEJ）腺癌的成年患者，这些患者根据DESTINY-Gastric01和/或DESTINY-Gastric02试验的结果接受了先前基于曲妥珠单抗的方案。。

ENHERTU (5.4 mg/kg) is approved in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials.

ENHERTU（5.4 mg/kg）在美国被批准用于治疗无法切除或转移性HER2阳性（IHC 3+）实体瘤的成年患者，这些患者先前接受过全身治疗，并且根据DESTINY-PanTumor02，DESTINY-Lung01和DESTINY-CRC02试验的疗效结果没有令人满意的替代治疗选择。

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial..

是否继续批准该适应症可能取决于验证性试验中临床益处的验证和描述。。

About the ENHERTU Clinical Development Program

关于ENHERTU临床开发计划

A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway.

一项全面的全球临床开发计划正在评估ENHERTU单药治疗多种HER2靶向癌症的疗效和安全性。与免疫疗法等其他抗癌治疗相结合的试验也正在进行中。

About the Daiichi Sankyo and AstraZeneca Collaboration

关于第一三共和阿斯利康的合作

Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan..

第一三共与阿斯利康于2019年3月达成全球合作，共同开发ENHERTU，并于2020年7月将其商业化，但在日本，第一三共对每个ADC拥有独家权利。Daiichi Sankyo负责ENHERTU和datopotamab deruxtecan的制造和供应。。

About the DXd ADC Portfolio of Daiichi Sankyo

关于第一三共的DXd ADC投资组合

The DXd ADC portfolio of Daiichi Sankyo currently consists of six ADCs in clinical development across multiple types of cancer. ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc., Rahway, N.J.

Daiichi Sankyo的DXd ADC组合目前由六个ADC组成，这些ADC在多种癌症的临床开发中。针对HER2的ADC ENHERTU和针对TROP2的ADC datopotamab deruxtecan（Dato DXd）正在与阿斯利康联合开发并在全球商业化。Patritumab deruxtecan（HER3 DXd），一种HER3导向的ADC，ifinatamab deruxtecan（I-DXd），一种B7-H3导向的ADC，以及raludotatug deruxtecan（R-DXd），一种CDH6导向的ADC，正在与Merck＆Co.，Inc.，Rahway，N.J.联合开发并在全球商业化。

USA. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo..

美国。DS-3939是一种TA-MUC1定向的ADC，由Daiichi Sankyo开发。。

Designed using Daiichi Sankyo’s proprietary DXd ADC Technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers..

使用Daiichi Sankyo专有的DXd ADC技术设计，以靶向并传递表达特定细胞表面抗原的癌细胞内的细胞毒性有效载荷，每个ADC由单克隆抗体组成，该单克隆抗体通过基于四肽的可切割接头连接到许多拓扑异构酶I抑制剂有效载荷（exatecan衍生物，DXd）。。

Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan and DS-3939 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.

Datopotamab deruxtecan，ifinatamab deruxtecan，patritumab deruxtecan，raludotatug deruxtecan和DS-3939是尚未在任何国家批准用于任何适应症的研究药物。安全性和有效性尚未确定。

ENHERTU U.S. Important Safety Information

ENHERTU美国重要安全信息

Indications

适应症

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

ENHERTU是一种HER2定向抗体和拓扑异构酶抑制剂偶联物，用于治疗成年患者：

Unresectable or metastatic HER2-positive (IHC 3+ or ISH positive) breast cancer who have received a prior anti-HER2-based regimen either:

先前接受过抗HER2方案的不可切除或转移性HER2阳性（IHC 3+或ISH阳性）乳腺癌：

In the metastatic setting, or

在转移性环境中，或

In the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy

在新辅助或辅助治疗中，并在完成治疗后的六个月内或六个月内出现疾病复发

Unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy

根据FDA批准的测试确定，不可切除或转移性HER2低（IHC 1+或IHC 2+/ISH-）乳腺癌，这些患者先前在转移性环境中接受过化疗，或者在完成辅助化疗后6个月内或6个月内出现疾病复发

Unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy

不可切除或转移的非小细胞肺癌（NSCLC），其肿瘤具有激活的HER2（ERBB2）突变，经FDA批准的测试检测，并且先前接受过全身治疗

This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

根据客观反应率和反应持续时间，加速批准该适应症。继续批准该适应症可能取决于验证性试验中临床益处的验证和描述。

Locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen

接受过曲妥珠单抗治疗的局部晚期或转移性HER2阳性（IHC 3+或IHC 2+/ISH阳性）胃或胃食管交界处（GEJ）腺癌

Unresectable or metastatic HER2-positive (IHC3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options

先前接受过全身治疗且没有令人满意的替代治疗选择的不可切除或转移性HER2阳性（IHC3+）实体瘤

根据客观反应率和反应持续时间，加速批准该适应症。继续批准该适应症可能取决于验证性试验中临床益处的验证和描述。

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

警告：间质性肺病和胚胎-胎儿毒性

Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis.

ENHERTU报道了间质性肺病（ILD）和肺炎，包括致命病例。监测并及时调查体征和症状，包括咳嗽、呼吸困难、发烧和其他新的或恶化的呼吸道症状。所有2级或更高ILD/肺炎患者永久停用ENHERTU。

Advise patients of the risk and to immediately report symptoms..

告知患者风险并立即报告症状。。

Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

怀孕期间接触ENHERTU会导致胚胎-胎儿伤害。告知患者这些风险以及有效避孕的必要性。

Contraindications

禁忌症

None.

没有。

Warnings and Precautions

警告和注意事项

Interstitial Lung Disease / Pneumonitis

间质性肺病/肺炎

Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms.

用ENHERTU治疗的患者可能会发生严重，危及生命或致命的间质性肺病（ILD），包括肺炎。中度肾功能不全患者的1级和2级ILD/肺炎发生率较高。建议患者立即报告咳嗽、呼吸困难、发烧和/或任何新的或恶化的呼吸道症状。

Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose.

监测患者的ILD体征和症状。及时调查ILD的证据。通过放射成像评估疑似ILD的患者。考虑咨询肺科医生。对于无症状ILD/肺炎（1级），中断ENHERTU直至解决至0级，然后如果在发病日期≤28天内解决，则维持剂量。

If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks..

如果在发病日期后>28天内解决，则减少剂量一级。一旦怀疑ILD/肺炎（例如，≥0.5 mg/kg/天泼尼松龙或等效物），就考虑使用皮质类固醇治疗。对于有症状的ILD/肺炎（2级或更高），永久停用ENHERTU。一旦怀疑ILD/肺炎（例如，≥1 mg/kg/天泼尼松龙或同等药物），立即开始全身皮质类固醇治疗，并持续至少14天，然后逐渐减量至少4周。。

HER2-Positive or HER2-Low Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)

HER2阳性或HER2低转移性乳腺癌，HER2突变NSCLC和实体瘤（包括IHC 3+）（5.4 mg/kg）

In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Median time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis occurred in 1.0% of patients treated with ENHERTU..

在用ENHERTU 5.4 mg/kg治疗的转移性乳腺癌，HER2突变型NSCLC和其他实体瘤患者中，ILD发生率为12%。首次发病的中位时间为5.5个月（范围：0.9至31.5）。1.0%接受ENHERTU治疗的患者因ILD和/或肺炎而致命。。

HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

HER2阳性的局部晚期或转移性胃癌（6.4 mg/kg）

In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21).

在用ENHERTU 6.4 mg/kg治疗的局部晚期或转移性HER2阳性胃腺癌或GEJ腺癌患者中，ILD发生率为10%。首次发病的中位时间为2.8个月（范围：1.2至21）。

Neutropenia

中性粒细胞减少

Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose.

用ENHERTU治疗的患者可能会出现严重的中性粒细胞减少症，包括发热性中性粒细胞减少症。在开始使用ENHERTU之前和每次给药之前以及根据临床指示监测全血细胞计数。对于3级中性粒细胞减少症（绝对中性粒细胞计数[ANC]<1.0至0.5 x 109/L），中断ENHERTU直至达到2级或更低，然后维持剂量。

For Grade 4 neutropenia (ANC <0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by one level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3º C or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by one level..

对于4级中性粒细胞减少症（ANC<0.5 x 109/L），中断ENHERTU直至达到2级或更低，然后将剂量减少一个水平。对于发热性中性粒细胞减少症（ANC<1.0 x 109/L，温度>38.3ºC或持续温度≥38ºC超过1小时），中断ENHERTU直至解决，然后将剂量减少一个水平。。

HER2-Positive or HER2-Low Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)

HER2阳性或HER2低转移性乳腺癌，HER2突变NSCLC和实体瘤（包括IHC 3+）（5.4 mg/kg）

In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 63% of patients. Seventeen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 939).

在用ENHERTU 5.4 mg/kg治疗的转移性乳腺癌，HER2突变型NSCLC和其他实体瘤患者中，据报道63%的患者中性粒细胞计数下降。17%的患者中性粒细胞计数降低了3或4级。中性粒细胞计数首次下降的中位时间为22天（范围：2至939）。

Febrile neutropenia was reported in 1% of patients..

据报道，1%的患者出现发热性中性粒细胞减少症。。

HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

HER2阳性的局部晚期或转移性胃癌（6.4 mg/kg）

In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187).

在用ENHERTU 6.4 mg/kg治疗的局部晚期或转移性HER2阳性胃腺癌或GEJ腺癌患者中，据报道72%的患者中性粒细胞计数减少。51%的患者中性粒细胞计数降低了3或4级。中性粒细胞计数首次下降的中位时间为16天（范围：4至187）。

Febrile neutropenia was reported in 4.8% of patients..

据报道，4.8%的患者出现发热性中性粒细胞减少症。。

Left Ventricular Dysfunction

左心室功能不全

Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated.

接受ENHERTU治疗的患者发生左心室功能障碍的风险可能会增加。用抗HER2疗法（包括ENHERTU）观察到左心室射血分数（LVEF）降低。根据临床指示，在开始ENHERTU之前和治疗期间定期评估LVEF。

Manage LVEF decrease through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks.

通过治疗中断管理LVEF降低。当LVEF>45%且从基线绝对下降10-20%时，继续用ENHERTU治疗。当LVEF为40-45%且从基线绝对下降小于10%时，继续使用ENHERTU治疗并在3周内重复LVEF评估。当LVEF为40-45%且从基线绝对下降为10-20%时，中断ENHERTU并在3周内重复LVEF评估。

If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks.

如果LVEF尚未从基线恢复到10%以内，则永久停用ENHERTU。如果LVEF从基线恢复到10%以内，则以相同剂量恢复用ENHERTU治疗。当LVEF小于40%或从基线绝对下降>20%时，中断ENHERTU并在3周内重复LVEF评估。

If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment..

如果LVEF小于40%或从基线绝对下降>20%，则永久停用ENHERTU。症状性充血性心力衰竭患者永久停用ENHERTU。在开始治疗之前，尚未对有临床显着心脏病史或LVEF<50%的患者进行ENHERTU治疗的研究。。

HER2-Positive or HER2-Low Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)

HER2阳性或HER2低转移性乳腺癌，HER2突变NSCLC和实体瘤（包括IHC 3+）（5.4 mg/kg）

In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, LVEF decrease was reported in 3.8% of patients, of which 0.6% were Grade 3.

在用ENHERTU 5.4 mg/kg治疗的转移性乳腺癌，HER2突变型NSCLC和其他实体瘤患者中，据报道3.8%的患者LVEF降低，其中0.6%为3级。

HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

HER2阳性的局部晚期或转移性胃癌（6.4 mg/kg）

In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF.

在用ENHERTU 6.4 mg/kg治疗的局部晚期或转移性HER2阳性胃腺癌或GEJ腺癌患者中，未报告心力衰竭的临床不良事件；然而，在超声心动图上，发现8%的LVEF无症状2级下降。

Embryo-Fetal Toxicity

胚胎-胎儿毒性

ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU.

给孕妇服用恩赫图会对胎儿造成伤害。告知患者胎儿的潜在风险。在开始ENHERTU之前，验证具有生殖潜力的女性的妊娠状况。建议有生殖潜力的女性在治疗期间和最后一剂ENHERTU后7个月内使用有效的避孕措施。

Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU..

建议有生殖潜力的女性伴侣的男性患者在使用ENHERTU治疗期间和最后一剂ENHERTU后4个月内使用有效的避孕措施。。

Additional Dose Modifications

额外剂量修改

Thrombocytopenia

血小板减少症

For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by one level.

对于3级血小板减少症（血小板<50至25 x 109/L），中断ENHERTU直至达到1级或更低，然后维持剂量。对于4级血小板减少症（血小板<25 x 109/L），中断ENHERTU直至达到1级或更低，然后将剂量减少一个水平。

Adverse Reactions

不良反应

HER2-Positive and HER2-Low Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)

HER2阳性和HER2低转移性乳腺癌，HER2突变NSCLC和实体瘤（包括IHC 3+）（5.4 mg/kg）

The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 1799 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Lung01, DESTINY-Lung02, DESTINY-CRC02, and DESTINY-PanTumor02. Among these patients, 65% were exposed for >6 months and 38% were exposed for >1 year.

汇总的安全人群反映了研究DS8201-A-J101（NCT02564900），DESTINY-Breast01，DESTINY-Breast02，DESTINY-Breast03，DESTINY-Breast04，DESTINY-Lung01，DESTINY-Lung02，DESTINY-CRC02和DESTINY-PanTumor02中1799名患者每3周静脉注射5.4 mg/kg。在这些患者中，65%暴露于>6个月，38%暴露于>1年。

In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (73%), decreased white blood cell count (70%), decreased hemoglobin (66%), decreased neutrophil count (63%), decreased lymphocyte count (58%), fatigue (56%), decreased platelet count (48%), increased aspartate aminotransferase (47%), increased alanine aminotransferase (43%), vomiting (40%), increased blood alkaline phosphatase (38%), alopecia (34%), constipation (33%), decreased appetite (32%), decreased blood potassium (31%), diarrhea (29%), musculoskeletal pain (24%), and abdominal pain (20%)..

在这个汇总的安全人群中，包括实验室异常在内的最常见（≥20%）的不良反应是恶心（73%），白细胞计数减少（70%），血红蛋白减少（66%），中性粒细胞计数减少（63%），淋巴细胞计数减少（58%），疲劳（56%），血小板计数减少（48%），天冬氨酸转氨酶增加（47%），丙氨酸转氨酶增加（43%），呕吐（40%），血液碱性磷酸酶增加（38%），脱发（34%），便秘（33%），食欲下降（32%），血钾减少（31%），腹泻（29%），肌肉骨骼疼痛（24%）和腹痛（20%）。。

HER2-Positive Metastatic Breast Cancer

HER2阳性转移性乳腺癌

DESTINY-Breast03

The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg intravenously once every three weeks in DESTINY-Breast03. The median duration of treatment was 14 months (range: 0.7 to 30).

在257例不可切除或转移性HER2阳性乳腺癌患者中评估了ENHERTU的安全性，这些患者在DESTINY-Breast03中每三周静脉注射至少一剂5.4 mg/kg的ENHERTU。中位治疗时间为14个月（范围：0.7至30）。

Serious adverse reactions occurred in 19% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were vomiting, interstitial lung disease, pneumonia, pyrexia, and urinary tract infection. Fatalities due to adverse reactions occurred in 0.8% of patients including COVID-19 and sudden death (one patient each)..

接受ENHERTU治疗的患者中有19%发生严重不良反应。接受ENHERTU治疗的患者中，>1%的严重不良反应是呕吐，间质性肺病，肺炎，发热和尿路感染。0.8%的患者因不良反应死亡，包括新型冠状病毒肺炎和猝死（各一名患者）。。

ENHERTU was permanently discontinued in 14% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 44% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, leukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis.

14%的患者永久停用ENHERTU，其中ILD/肺炎占8%。44%接受ENHERTU治疗的患者因不良反应而发生剂量中断。与剂量中断相关的最常见不良反应（>2%）是中性粒细胞减少症，白细胞减少症，贫血，血小板减少症，肺炎，恶心，疲劳和ILD/肺炎。

Dose reductions occurred in 21% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, neutropenia, and fatigue..

21%接受ENHERTU治疗的患者剂量减少。与剂量减少相关的最常见不良反应（>2%）是恶心，中性粒细胞减少和疲劳。。

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (74%), decreased neutrophil count (70%), increased aspartate aminotransferase (67%), decreased hemoglobin (64%), decreased lymphocyte count (55%), increased alanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%), vomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%), decreased blood potassium (35%), constipation (34%), musculoskeletal pain (31%), diarrhea (29%), decreased appetite (29%), headache (22%), respiratory infection (22%), abdominal pain (21%), increased blood bilirubin (20%), and stomatitis (20%)..

最常见的（≥20%）不良反应包括实验室异常，包括恶心（76%），白细胞计数减少（74%），中性粒细胞计数减少（70%），天冬氨酸转氨酶增加（67%），血红蛋白减少（64%），淋巴细胞计数减少（55%），丙氨酸转氨酶增加（53%），血小板计数减少（52%），疲劳（49%），呕吐（49%），血液碱性磷酸酶增加（49%），脱发（37%），血钾减少（35%），便秘（34%），肌肉骨骼疼痛（31%），腹泻（29%），食欲下降（29%），头痛（22%），呼吸道感染（22%），腹痛（21%），血胆红素增加（20%）和口腔炎（20%）。。

HER2-Low Metastatic Breast Cancer

HER2低转移性乳腺癌

DESTINY-Breast04

The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast04. The median duration of treatment was 8 months (range: 0.2 to 33) for patients who received ENHERTU..

对371例不可切除或转移性HER2低（IHC 1+或IHC 2+/ISH-）乳腺癌患者进行了ENHERTU的安全性评估，这些患者在DESTINY-Breast04中每3周静脉注射ENHERTU 5.4 mg/kg。接受ENHERTU治疗的患者的中位治疗时间为8个月（范围：0.2至33）。。

Serious adverse reactions occurred in 28% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to adverse reactions occurred in 4% of patients including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion, and respiratory failure (1 patient each)..

接受ENHERTU治疗的患者中有28%发生严重不良反应。接受ENHERTU治疗的患者中，>1%的严重不良反应是ILD/肺炎，肺炎，呼吸困难，肌肉骨骼疼痛，败血症，贫血，发热性中性粒细胞减少症，高钙血症，恶心，发热和呕吐。4%的患者因不良反应死亡，包括ILD/肺炎（3例）；败血症（2例）；和缺血性结肠炎，弥散性血管内凝血，呼吸困难，发热性中性粒细胞减少症，一般身体健康恶化，胸腔积液和呼吸衰竭（各1例）。。

ENHERTU was permanently discontinued in 16% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 39% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia.

16%的患者永久停用ENHERTU，其中ILD/肺炎占8%。39%接受ENHERTU治疗的患者因不良反应而发生剂量中断。与剂量中断相关的最常见不良反应（>2%）是中性粒细胞减少症，疲劳，贫血，白细胞减少症，COVID-19，ILD/肺炎，转氨酶升高和高胆红素血症。

Dose reductions occurred in 23% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, thrombocytopenia, and neutropenia..

23%接受ENHERTU治疗的患者剂量减少。与剂量减少相关的最常见不良反应（>2%）是疲劳，恶心，血小板减少和中性粒细胞减少。。

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (70%), decreased hemoglobin (64%), decreased neutrophil count (64%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (44%), alopecia (40%), vomiting (40%), increased aspartate aminotransferase (38%), increased alanine aminotransferase (36%), constipation (34%), increased blood alkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain (32%), diarrhea (27%), and decreased blood potassium (25%)..

最常见的（≥20%）不良反应包括实验室异常，包括恶心（76%），白细胞计数减少（70%），血红蛋白减少（64%），中性粒细胞计数减少（64%），淋巴细胞计数减少（55%），疲劳（54%），血小板计数减少（44%），脱发（40%），呕吐（40%），天冬氨酸转氨酶增加（38%），丙氨酸转氨酶增加（36%），便秘（34%），血液碱性磷酸酶增加（34%），食欲下降（32%），肌肉骨骼疼痛（32%），腹泻（27%）和血钾减少（25%）。。

HER2-Mutant Unresectable or Metastatic NSCLC (5.4 mg/kg)

HER2突变不可切除或转移性NSCLC（5.4 mg/kg）

DESTINY-Lung02 evaluated two dose levels (5.4 mg/kg [n=101] and 6.4 mg/kg [n=50]); however, only the results for the recommended dose of 5.4 mg/kg intravenously every 3 weeks are described below due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis..

DESTINY-Lung02评估了两种剂量水平（5.4 mg/kg[n=101]和6.4 mg/kg[n=50]）；然而，由于在NSCLC患者（包括ILD/肺炎）中观察到较高剂量的毒性增加，因此每3周静脉注射推荐剂量5.4 mg/kg的结果如下所述。。

The safety of ENHERTU was evaluated in 101 patients with HER2-mutant unresectable or metastatic NSCLC who received ENHERTU 5.4 mg/kg intravenously once every three weeks until disease progression or unacceptable toxicity in DESTINY‑Lung02. Nineteen percent of patients were exposed for >6 months.

对101例HER2突变不可切除或转移性NSCLC患者进行了ENHERTU的安全性评估，这些患者每三周静脉注射ENHERTU 5.4 mg/kg，直至疾病进展或DESTINY-Lung02出现不可接受的毒性。19%的患者暴露时间超过6个月。

Serious adverse reactions occurred in 30% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, thrombocytopenia, dyspnea, nausea, pleural effusion, and increased troponin I. Fatality occurred in 1 patient with suspected ILD/pneumonitis (1%)..

接受ENHERTU治疗的患者中有30%发生严重不良反应。接受ENHERTU治疗的患者中，>1%的严重不良反应为ILD/肺炎，血小板减少，呼吸困难，恶心，胸腔积液和肌钙蛋白I升高。1例疑似ILD/肺炎患者（1%）死亡。。

ENHERTU was permanently discontinued in 8% of patients. Adverse reactions which resulted in permanent discontinuation of ENHERTU were ILD/pneumonitis, diarrhea, decreased blood potassium, hypomagnesemia, myocarditis, and vomiting. Dose interruptions of ENHERTU due to adverse reactions occurred in 23% of patients.

8%的患者永久停用ENHERTU。导致永久停用ENHERTU的不良反应是ILD/肺炎，腹泻，血钾降低，低镁血症，心肌炎和呕吐。23%的患者因不良反应而中断了ENHERTU的剂量。

Adverse reactions which required dose interruption (>2%) included neutropenia and ILD/pneumonitis. Dose reductions due to an adverse reaction occurred in 11% of patients..

需要中断剂量（>2%）的不良反应包括中性粒细胞减少症和ILD/肺炎。11%的患者因不良反应而减少剂量。。

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (61%), decreased white blood cell count (60%), decreased hemoglobin (58%), decreased neutrophil count (52%), decreased lymphocyte count (43%), decreased platelet count (40%), decreased albumin (39%), increased aspartate aminotransferase (35%), increased alanine aminotransferase (34%), fatigue (32%), constipation (31%), decreased appetite (30%), vomiting (26%), increased alkaline phosphatase (22%), and alopecia (21%)..

包括实验室异常在内的最常见（≥20%）不良反应是恶心（61%），白细胞计数减少（60%），血红蛋白减少（58%），中性粒细胞计数减少（52%），淋巴细胞计数减少（43%），血小板计数减少（40%），白蛋白减少（39%），天冬氨酸转氨酶增加（35%），丙氨酸转氨酶增加（34%），疲劳（32%），便秘（31%），食欲下降（30%），呕吐（26%），碱性磷酸酶增加（22%）和脱发（21%）。。

HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

HER2阳性的局部晚期或转移性胃癌（6.4 mg/kg）

The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least one dose of either ENHERTU (N=125) 6.4 mg/kg every 3 weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2 weekly for 3 weeks.

在DESTINY-Gastric01中，对187例局部晚期或转移性HER2阳性胃腺癌或GEJ腺癌患者评估了ENHERTU的安全性。患者每3周静脉注射至少一剂ENHERTU（N=125）6.4 mg/kg或伊立替康（N=55）150 mg/m2，每两周或紫杉醇（N=7）80 mg/m2，持续3周。

The median duration of treatment was 4.6 months (range: 0.7 to 22.3) for patients who received ENHERTU..

接受ENHERTU治疗的患者的中位治疗时间为4.6个月（范围：0.7至22.3）。。

Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in one patient each (0.8%)..

接受ENHERTU 6.4 mg/kg治疗的患者中有44%发生严重不良反应。>2%接受ENHERTU治疗的患者的严重不良反应是食欲下降，ILD，贫血，脱水，肺炎，胆汁淤积性黄疸，发热和肿瘤出血。2.4%的患者因不良反应死亡：弥散性血管内凝血、大肠穿孔和肺炎各发生1例（0.8%）。。

ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and decreased blood potassium.

15%的患者永久停用ENHERTU，其中ILD占6%。62%接受ENHERTU治疗的患者因不良反应而发生剂量中断。与剂量中断相关的最常见不良反应（>2%）是中性粒细胞减少症，贫血，食欲下降，白细胞减少症，疲劳，血小板减少症，ILD，肺炎，淋巴细胞减少症，上呼吸道感染，腹泻和血钾降低。

Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia..

32%接受ENHERTU治疗的患者剂量减少。与剂量减少相关的最常见不良反应（>2%）是中性粒细胞减少症，食欲下降，疲劳，恶心和发热性中性粒细胞减少症。。

The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (75%), decreased white blood cell count (74%), decreased neutrophil count (72%), decreased lymphocyte count (70%), decreased platelet count (68%), nausea (63%), decreased appetite (60%), increased aspartate aminotransferase (58%), fatigue (55%), increased blood alkaline phosphatase (54%), increased alanine aminotransferase (47%), diarrhea (32%), decreased blood potassium (30%), vomiting (26%), constipation (24%), increased blood bilirubin (24%), pyrexia (24%), and alopecia (22%)..

包括实验室异常在内的最常见（≥20%）不良反应是血红蛋白降低（75%），白细胞计数降低（74%），中性粒细胞计数降低（72%），淋巴细胞计数降低（70%），血小板计数降低（68%），恶心（63%），食欲下降（60%），天冬氨酸转氨酶升高（58%），疲劳（55%），血液碱性磷酸酶升高（54%），丙氨酸转氨酶升高（47%），腹泻（32%），血钾降低（30%），呕吐（26%），便秘（24%），血胆红素升高（24%），发热（24%）和脱发（22%）。。

HER2-Positive (IHC3+) Unresectable or Metastatic Solid Tumors

HER2阳性（IHC3+）不可切除或转移性实体瘤

The safety of ENHERTU was evaluated in 347 adult patients with unresectable or metastatic HER2-positive (IHC3+) solid tumors who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast01, DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02. The median duration of treatment was 8.3 months (range 0.7 to 30.2)..

在347例不可切除或转移性HER2阳性（IHC3+）实体瘤的成年患者中评估了ENHERTU的安全性，这些患者每3周在DESTINY-Breast01，DESTINY-PanTumor02，DESTINY-Lung01和DESTINY-CRC02中静脉注射ENHERTU 5.4 mg/kg。中位治疗时间为8.3个月（范围0.7至30.2）。。

Serious adverse reactions occurred in 34% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were sepsis, pneumonia, vomiting, urinary tract infection, abdominal pain, nausea, pneumonitis, pleural effusion, hemorrhage, COVID-19, fatigue, acute kidney injury, anemia, cellulitis, and dyspnea.

34%接受ENHERTU治疗的患者发生严重不良反应。接受ENHERTU治疗的患者中，>1%的严重不良反应为败血症，肺炎，呕吐，尿路感染，腹痛，恶心，肺炎，胸腔积液，出血，新型冠状病毒，疲劳，急性肾损伤，贫血，蜂窝织炎和呼吸困难。

Fatalities due to adverse reactions occurred in 6.3% of patients including ILD/pneumonitis (2.3%), cardiac arrest (0.6%), COVID-19 (0.6%), and sepsis (0.6%). The following events occurred in one patient each (0.3%): acute kidney injury, cerebrovascular accident, general physical health deterioration, pneumonia, and hemorrhagic shock..

6.3%的患者因不良反应死亡，包括ILD/肺炎（2.3%），心脏骤停（0.6%），新型冠状病毒肺炎（0.6%）和败血症（0.6%）。以下事件发生在每位患者中（0.3%）：急性肾损伤，脑血管意外，一般身体健康恶化，肺炎和失血性休克。。

ENHERTU was permanently discontinued in 15% of patients, of which ILD/pneumonitis accounted for 10%. Dose interruptions due to adverse reactions occurred in 48% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were decreased neutrophil count, anemia, COVID-19, fatigue, decreased white blood cell count, and ILD/pneumonitis.

15%的患者永久停用ENHERTU，其中ILD/肺炎占10%。48%的患者因不良反应而中断剂量。与剂量中断相关的最常见不良反应（>2%）是中性粒细胞计数减少，贫血，新型冠状病毒肺炎，疲劳，白细胞计数减少和ILD/肺炎。

Dose reductions occurred in 27% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, decreased neutrophil count, ILD/pneumonitis, and diarrhea..

用ENHERTU治疗的患者中有27%发生剂量减少。与剂量减少相关的最常见不良反应（>2%）是疲劳，恶心，中性粒细胞计数减少，ILD/肺炎和腹泻。。

The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (75%), nausea (69%), decreased hemoglobin (67%), decreased neutrophil count (66%), fatigue (59%), decreased lymphocyte count (58%), decreased platelet count (51%), increased aspartate aminotransferase (45%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (36%), vomiting (35%), decreased appetite (34%), alopecia (34%), diarrhea (31%), decreased blood potassium (29%), constipation (28%), decreased sodium (22%), stomatitis (20%), and upper respiratory tract infection (20%)..

包括实验室异常在内的最常见（≥20%）的不良反应是白细胞计数减少（75%），恶心（69%），血红蛋白减少（67%），中性粒细胞计数减少（66%），疲劳（59%），淋巴细胞计数减少（58%），血小板计数减少（51%），天冬氨酸转氨酶增加（45%），丙氨酸转氨酶增加（44%），血液碱性磷酸酶增加（36%），呕吐（35%），食欲下降（34%），脱发（34%），腹泻（31%），血钾减少（29%），便秘（28%），钠减少（22%），口腔炎（20%）和上呼吸道感染（20%）。。

Use in Specific Populations

在特定人群中使用

Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months after the last dose of ENHERTU.

怀孕：恩赫图给孕妇服用时会对胎儿造成伤害。告知患者胎儿的潜在风险。如果孕妇使用ENHERTU，或者患者在最后一剂ENHERTU后7个月内怀孕，则有临床考虑因素。

Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose..

哺乳期：没有关于母乳中ENHERTU的存在，对母乳喂养的孩子的影响或对产奶量的影响的数据。由于母乳喂养的孩子可能会产生严重的不良反应，因此建议女性在使用ENHERTU治疗期间以及最后一次服用后7个月内不要母乳喂养。。

Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for 7 months after the last dose.

生殖潜能的女性和男性：妊娠测试：在开始ENHERTU之前验证生殖潜能女性的妊娠状况。避孕方法：女性：ENHERTU给孕妇服用时会对胎儿造成伤害。建议有生殖潜力的女性在使用ENHERTU治疗期间和最后一剂后7个月内使用有效的避孕方法。

Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose. Infertility: ENHERTU may impair male reproductive function and fertility..

男性：建议有生殖潜力的女性伴侣的男性患者在使用ENHERTU治疗期间和最后一剂后4个月内使用有效的避孕方法。不育症：ENHERTU可能会损害男性的生殖功能和生育能力。。

Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.

儿科使用：ENHERTU的安全性和有效性尚未在儿科患者中确定。

Geriatric Use: Of the 1287 patients with HER2-positive or HER2-low breast cancer treated with ENHERTU 5.4 mg/kg, 22% were ≥65 years and 3.8% were ≥75 years. No overall differences in efficacy within clinical studies were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (59%) as compared to younger patients (49%).

老年使用：在用ENHERTU 5.4 mg/kg治疗的1287例HER2阳性或HER2低乳腺癌患者中，22%的患者≥65岁，3.8%的患者≥75岁。与年轻患者相比，≥65岁的患者在临床研究中没有观察到总体疗效差异。与年轻患者（49%）相比，≥65岁患者（59%）观察到的3-4级不良反应发生率更高。

Of the 101 patients with HER2-mutant unresectable or metastatic NSCLC treated with ENHERTU 5.4 mg/kg, 40% were ≥65 years and 8% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 125 patients with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years.

在用ENHERTU 5.4 mg/kg治疗的101例HER2突变不可切除或转移性NSCLC患者中，40%的患者≥65岁，8%的患者≥75岁。与年轻患者相比，≥65岁的患者在疗效或安全性方面没有观察到总体差异。在DESTINY-Gastric01中用ENHERTU 6.4 mg/kg治疗的125例HER2阳性局部晚期或转移性胃腺癌或GEJ腺癌患者中，56%≥65岁，14%≥75岁。

No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 192 patients with HER2-positive (IHC 3+) unresectable or metastatic solid tumors treated with ENHERTU 5.4 mg/kg in DESTINY-PanTumor02, DESTINY-Lung01, or DESTINY-CRC02, 39% were 65 years or older and 9% were 75 years or older.

与年轻患者相比，≥65岁的患者在疗效或安全性方面没有观察到总体差异。在DESTINY-PanTumor02，DESTINY-Lung01或DESTINY-CRC02中，用ENHERTU 5.4 mg/kg治疗的192例HER2阳性（IHC 3+）不可切除或转移性实体瘤患者中，39%为65岁或以上，9%为75岁或以上。

No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients..

与年轻患者相比，≥65岁的患者在疗效或安全性方面没有总体差异。。

Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Monitor patients with moderate renal impairment more frequently. The recommended dosage of ENHERTU has not been established for patients with severe renal impairment (CLcr <30 mL/min)..

肾功能不全：中度肾功能不全患者的1级和2级ILD/肺炎发生率较高。更频繁地监测中度肾功能不全患者。对于严重肾功能不全（CLcr<30 mL/min）的患者，尚未确定ENHERTU的推荐剂量。。

Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor, DXd. The recommended dosage of ENHERTU has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST)..

肝损伤：对于中度肝损伤患者，由于可能增加暴露，密切监测与拓扑异构酶抑制剂DXd相关的毒性增加。对于严重肝功能损害（总胆红素>3倍ULN和任何AST）的患者，尚未确定ENHERTU的推荐剂量。。

To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.

要报告疑似不良反应，请联系Daiichi Sankyo，Inc.，电话1-877-437-7763或FDA，电话1-800-FDA-1088或FDA.gov/medwatch。

Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

请参阅随附的完整处方信息，包括盒装警告和药物指南。

About Daiichi Sankyo

关于第一三共

Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need.

Daiichi Sankyo是一家创新的全球医疗保健公司，致力于社会的可持续发展，发现、开发和提供新的护理标准，以丰富世界各地的生活质量。拥有120多年的经验，第一三共利用其世界一流的科学和技术，为癌症，心血管疾病和其他医疗需求未得到满足的疾病患者创造新的模式和创新药物。

For more information, please visit www.daiichisankyo.com..

欲了解更多信息，请访问www.daiichisankyo.com。。

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References

参考文献

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Bray F等人，CA癌症J临床。2024年；10.3322/CAAC.21834。

2 National Cancer Institute. SEER Cancer Stat Facts: Female Breast Cancer Subtypes. Accessed May 2024.

2国家癌症研究所。SEER癌症统计事实：女性乳腺癌亚型。2024年5月访问。

3 Iqbal N, et al. Mol Biol Int. 2014;852748.

3 Iqbal N等人，《摩尔国际》，2014年；852748.