TOKYO&BASKING RIDGE，N.J.--（BUSINESS WIRE）--Positive topline results from theDESTINY-Breast06phase3trial 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 the primary trial population of patients with HR positive，HER2low（IHC1+or IHC2+/ISH-）metastatic breast cancer following one or more lines of endocrine therapy。
statistically significant and clinically meaningful improvement in PFS also was observed in the overall trial population（patients with HER2 low and HER2 ultralow[defined as IHC0 with membrane staining；IHC>0<1+]metatic breast cancer。A pre-specified subgroup analysis showed that the clinically meaningful improvement was consistent between patients with HER2low and HER2 ultralow expression。
Overall survival（OS）data were not mature at the time of the analysis。However，ENHERTU showed an early trend towards an OS improvement versus standard of care chemotherapy in patients with HER2low metatic breast cancer and in the overall trial population.The trial will continue as planned to further assess OS and other secondary endpoints。
ENHERTU is aspecifically engineered HER2directed DXd antibody drug conjugate（ADC）discovered by Daiichi Sankyo（TSE:4568）and being jointly developed and commercialized byDaiichi Sankyoand，andAstraZeneca（LSE/STO/Nasdaq:AZN）。
It is estimated that approximately60%to65%of HR positive，HER2negative breast cancers are HER2low and potentially an additional25%may be HER2ultralow。1,2Endocrine therapies are widely used in the early lines of treatment for HR positive metatic breast cancer.However，after two lines of treatment，further efficacy from endocrine therapy is often limited。3The current standard of care following endocrine therapy is chemotherapy，which is associated with poor response rates and outcomes。3,4,5,6
“DESTINY-Breast06high light the importance of continuing to challenge current treatment paradigms and established breast cancer classifications to evolve how we treat patients with HR positive，HER2expressing metastatic breast cancer，“said Ken Takeshita，MD，Global Head，R&D，Daiichi Sankyo.”Building on the practice-changing data seen in DESTINY-Breast04，these results reinforce the potential foruse of ENHERTU earlier in the treatment landscape and in an even broader patient population.”
“DESTINY-Breast06 shows that ENHERTU could become a new standard of care for patients with HER2 low and HER2 ultralow metatic breast cancer following one or more lines of endocrine therapy，”said Susan Galbraith，MBBChir，PhD，Executive Vice President，Oncology R&D，AstraZeneca.“These data underscore the potential for treatment with ENHERTU across the spectrum of HR positive breast cancer，further redefining the treatment of metastatic breast cancer.”
The safety profile of ENHERTU was consistent with previous breast cancer clinical trials with no new safety signals identified。
Data from DESTINY-Breast06will be presented at an upcoming medical meeting and shared with global regulatory authorities。
About DESTINY-Breast06
DESTINY-Breast06is a global，randomized，open-label，phase3trial evaluating the efficacy and safety of ENHERTU（5.4mg/kg）versus investigator’s choice of chemotherapy（capecitabine，paclitaxel or nab-paclitaxel）in patients with HR positive，HER2low（IHC1+or IHC2+/ISH-）or HER2ultralow（defined asIHC0with membrane staining[IHC>0<1+]）advanced or metatic breast cancer。Patients in the trial had no prior chemotherapy for advanced or metatic disease and either experienced disease progression within six months of starting first-line treatment with an endocrine therapy combined with a CDK4/6inhibitor received at least two previous lines lines of endocrine therapy the metasting。
The primary endpoint is PFS in the HR positive，HER2low patient population as measured by blinded independent central review（BICR）。Key secondary endpoints include OS in patients with HER2low expression and PFS by BICR and OS in the overall trial population（HER2low and HER2 ultralow）。Other secondary endpoints include objective response rate，duration of response，time to first subsequent treatment or death，time to second subsequent treatment or death and safety.Analysis of the HER2 ultralow subgroup was not powered to demonstrate statistical significance。
DESTINY-Breast06enrolled866 patients（n=713 for HER2low and n=153for HER2ultralow）at multiple sites in Asia，Europe，North America and South America.For more information about the trial，visitClinicalTrials.gov。
About Breast Cancer and HER2 Expression
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide。7ore than two million breast cancer cases were diagnosed in 2022 with more than665000 deaths globally。7While survival rates are high for those diagnosed with early breast cancer，only approximately30%of patients who are diagnosed with or progress to metastatic disease are expected to live five years after their diagnosis。8个
HR positive，HER2negative is the most common breast cancer subtype，accounting for approximately70%of all breast cancers。8个HER2is atyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors，including breast cancer。9Patients with high levels of HER2expression（IHC3+or IHC2+/ISH+）are classified as HER2positive and treated with HER2targeted therapies，representing approximately15to20%percent of all breast cancers。10Historically，tumors that were not classified as HER2positive were classified as HER2negative；however，many of these tumors still carry some level of HER2expression。11It is estimated that approximately60%to65%of HR positive，HER2negative breast cancers are HER2low and potentially an additional25%may be HER2ultralow。1,2
Prior to the approval of ENHERTU in HER2low metatic breast cancer post chemotherapy based on the DESTINY-Breast04trial，there were no targeted therapies approved specifically for patients with HER2low expression。12There are no targeted therapies specifically approved for patients with HER2ultralow expression。13
About ENHERTU
ENHERTU（trastuzumab deruxtecan；fam-trastuzumab deruxtecan-nxki in the U.S.only）is a HER2directed 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 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（5.4mg/kg）is approved in more than60 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2positive（IHC3+or IHC2+/原位hybridization（ISH）+）breast cancer who have received a prior anti-HER2-based regimen，either in the metatic 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 theDESTINY-Breast03trial。
ENHERTU（5.4mg/kg）is approved in more than55 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2low（IHC1+or IHC2+/（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 theDESTINY-Breast04trial。
ENHERTU（5.4mg/kg）is approved in more than35 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activatingHER2（ERBB2）mutations，应注意的是，应注意的是，应注意的是，应注意的是，应注意的是 DESTINY-Lung02trial.Continued approval in the U.S.for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial。
ENHERTU（6.4mg/kg）is approved in more than45 countries worldwide for the treatment of adult patients with locally advanced or metatic HER2positive（IHC3+or IHC2+/ISH+）gastric or gastroesophageal junction（GEJ）adenocarcinoma who have received a prior trastuzuma-basedDESTINY-Gastric01and/orDESTINY-Gastric02trials。
ENHERTU（5.4mg/kg）is approved in the U.S.for the treatment of adult patients with unresectable or metastatic HER2positive（IHC3+）solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficy resus lt from theDESTINY-PanTumor02单击功能区上，DESTINY-Lung01and，andDESTINY-CRC02trials.Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial。
About the ENHERTU Clinical Development Program
A comprehensive global clinical development program is underway evaluating the efficicacy and safety of ENHERTU monotherapy across multiple HER2targetable cancers.Trials in combination with other anticancer treatments，such as immunotherapy，also are underway。
About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into aglobal collaboration to jointly develop and commercialize ENHERTU inMarch2019and datopotamab deruxtecan inJuly2020单击功能区上，except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC.Daiichi Sankyo is responsible for the manufacturing and suply of ENHERTU and datopotamab deruxtecan。
About the DXd ADC Portfolio of Daiichi Sankyo
The DXd ADC portfolio of Daiichi Sankyo currently consists of six ADCs in clinical development across multiple types of cancer.ENHERTU，a HER2directed ADC，and datopotamab deruxtecan ruxtecan（HER3-DXd），a HER3 directed ADC，ifinatamab deruxtecan（I-DXd），aB7-H3 directed ADC，and raludotatug deruxtecan（R-DXd），aCDH6directed ADC，are being jointly developed and commercialized globally with Merck&Co.，Inc.，Rahway，N.J.USA.DS-3939，aTA-MUC1directed ADC，is being developed by Daiichi Sankyo。
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 monocloal antibody attached to a number of topoisomerase I inhibitor payloads，DXd）via tetrapeptide-based cleavable linkers。
Datopotamab deruxtecan，ifinatamab deruxtecan，patritumab deruxtecan，raludotatug deruxtecan and DS-3939are investigational medicines that have not been approved forany indication in any country.Safety and efficacy have not been established。
ENHERTU U.S.Important Safety Information
Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:
- Unresectable or metatic HER2-positive 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
- Unresectable or metastatic HER2-low（IHC1+or IHC2+/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 within6 months of completing adjuvant chemotherapy
- NSCLC whose tumors have activating HER2 mutations，经检测的FDA-approved测试和who have received a prior systemic therapy
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。
- 本地advanced or metatic HER2-positive（IHC3+or IHC2+/ISH positive）gastric or gastroesophageal junction（GEJ）adenocarcinoma who have received a prior trastuzuma-based regimen
- 不可分割或metatic HER2-positive（IHC3+）solid tumors who have receive d prior system ic treatment and have no satis factory alternative treatment options
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。
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WARNING:INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY
- Interstial 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 port symptoms.Permanently discontinue ENHERTU in all patients with Grade2 or higher ILD/pneumitis.Advise of reskries and the symptoms。
- Exposure to ENHERTU during pregnancy can cause embryo-fetal harm.Advise patients of these risks and the need for effective contraception。
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Contraindications
None。
Warnings and Precautions
中间Lung Disease/Pneumonitis
Severe，life-threatening，or fatal interstital lung disease（ILD），including pneumonitis，can occur in patients treated with ENHERTU.A higher incidence of Grade1and2ILD/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.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 pulmonogist.For asymptomatic ILD/pneumonitis（Grade1），interrupt ENHERTU until resolved to Grade0，then if resolved in≤28days from date of onset，maintain dose.If resolved in>28days from date of onset，reduce dose one level.Consider corticosteroid treatment assoon as ILD/pneumonitis suspected（e.g.，≥0.5mg/kg/day rednillone）。For symptomatic ILD/pneumonitis（Grade2 or greater），permanently discontinue ENHERTU.Promptly initiate systemic corticosteroid treatment assoon as ILD/pneumonitis suspected（e.g.，≥1mg/kg/day prednisolone or equivalent）and continue for at least14days followed by grapertaal for。
HER2-Mutant NSCLC，and Solid Tumors（Including IHC3+）（5.4mg/kg）
In patients with metastatic breast cancer，HER2-mutant NSCLC，and other solid tumors treated with ENHERTU5.4mg/kg，ILD occurred in12%of patients.Median time to first onset was5.5months（range:0.9 to 31.5）。Fatal outcomes due to ILD and/or pneumonitis occurred in 1.0%of patients treated with ENHERTU。
HER2-Positive Locally Advanced or Metastatic Gastric Cancer（6.4mg/kg）
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU6.4mg/kg，ILD occurred in10%of patients.Median time to first onset was2.8months（range:1.2to21）。
Neutropenia
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 Grade3neutropenia（Absolute Neutrophil Count[ANC]<1.0 to 0.5×109/L），interrupt ENHERTU until resolved to Grade2or less，then maintain dose.For Grade4neutropenia（ANC<0.5×109/L），interrupt ENHERTU until resolved to Grade2or less，then reduce dose by one level.For febrile neutropenia（ANC<1.0x109/L and temperature>38.3ºor a sustained temperature of≥38ºC for more than1 hour），interrupt ENHERTU until resolved，then reduce dose by one level。
HER2-Mutant NSCLC，and Solid Tumors（Including IHC3+）（5.4mg/kg）
In patients with metastatic breast cancer，HER2-mutant NSCLC，and other solid tumors treated with ENHERTU5.4mg/kg，a decrease in neutrophil count was reported in63%of patients.Seventeen percent had Grade3or4decreased neutrophil count.Median time to first onset of decreaten percent had Grade 3or4decreased neutrosed neutrophils count.to939）。Febrile neutropenia was reported in1%of patients。
HER2-Positive Locally Advanced or Metastatic Gastric Cancer（6.4mg/kg）
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU6.4mg/kg，adecrease in neutrophil count was reported in72%of patients.Fifty-one percent had Grade3or4decreased neutrophil count.Median time to first onset of creased needs e:4to187）。Febrile neutropenia was reported in 4.8%of patients。
左Ventricular Dysfunction
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-HER2therapies，including ENHERTU.Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated.Manage LVEF decrease through treatment interruption.When LVEF is>45%and absolute decrease from baseline is10-20%，continue treatment with ENHERTU.When LVEis F-45%from 10%，10%， continue treatment with ENHERTU and repeat LVEF assessment within3weeks.When LVEF is 40-45%and absolute decrease from baseline is10-20%，interrupt ENHERTU and repeat LVEF assessment within3weeks.If LVEF has not recovered to within10%from baseline，permanently discontinue HEENRTU.If ine， 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 within3weeks.If LVEF of<40%or absolute decrease from baseof>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。
HER2-Mutant NSCLC，and Solid Tumors（Including IHC3+）（5.4mg/kg）
In patients with metastatic breast cancer，HER2-mutant NSCLC，and other solid tumors treated with ENHERTU5.4mg/kg，LVEF decrease was reported in 3.8%of patients，of which0.6%were Grade3。
HER2-Positive Locally Advanced or Metastatic Gastric Cancer（6.4mg/kg）
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU6.4mg/kg，no clinical adverse events of heart failure were reported；however，on echocardiography，8%were found to have asymptomatic Grade2decrease in LVEF。
Embryo-Fatal Toxicity
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 dueament and the initation of the most ofENHERTU.Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4months after the last dose of ENHERTU。
Additional Dose Modifications
Thrombocytopenia
For Grade3thrombocytopenia（platelets<50to25x109/L）interrupt ENHERTU until resolved to Grade1 or less，then maintain dose.For Grade4thrombocytopenia（platelets<25x109/L）interrupt ENHERTU until resolved to Grade1 or less，then reduce dose by one level。
Adverse Reactions
HER2-Mutant NSCLC，and Solid Tumors（Including IHC3+）（5.4mg/kg）
The pooled safety population reflects exposure to ENHERTU5.4mg/kg intravenously every3weeks in1799 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>6months and 38%were exposed for>1year.In thpooled safetoled safepty（≥20%）se 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 aspartaaminotranse，insed 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%）。
HER2-定位金属断路器
DESTINY-Breast03
The safety of ENHERTU was evaluated in 257 patients with unresectable or metatic HER2-positive breast cancer who received at least one dose of ENHERTU5.4mg/kg intravenously once every three weeks in DESTINY-Breast03.The median duration of treatment was14months（range:0.7to30）。
Serious adverse reactions occurred in19%of patients receiving ENHERTU.Serious adverse reactions in>1%of patients who received ENHERTU were vomiting，interstial lung disease，pneumonia，pyrexia，and urinary tract infection.Fatalities due to adverse reactions occurred in 0.8%of patients including COVID-19and sudden death（one patient each）。
ENHERTU was permanently discontinued in 14%of patients，of which ILD/pneumonitis accounted for8%.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.Dose reductions occurred in21%of patients treated with ENHERTU.The most frequent adverse reactions（>2%）associated with dose reduction were nausea，neutropenia，and fatigue。
Themost 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（unt）nsferase（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 21%），increased blood bilirubin（20%），and stomatitis（20%）。
HER2-Low Metastatic Breast Cancer
DESTINY-Breast04
The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low（IHC1+or IHC2+/ISH-）breast cancer who received ENHERTU5.4mg/kg intravenously once every3 weeks in DESTINY-Breast04。The median duration of treatment was8months（range:0.2to33）for patients who received ENHERTU。
Serious adverse reactions occurred in28%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，reyxia，and vomiting.Fatalities due to adverse reactions occurred in4%of patients including ILD/pneumonitis（3patients）；sepsis（2patients）；and ischemic colitis，disseminated intravascular coagulation，dyspnea，febrile neutropenia，general physical health deterioration，pleural effusion，and respiratory failure（1patient each）。
ENHERTU was permanently discontinued in 16%of patients，of which ILD/pneumonitis accounted for8%.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.Dose reductions occurred in23%of patients treated with ENHERTU.The most frequent adverse reactions（>2%）associated with dose reduction were fatigue，nausea，thrombocytopenia，and neutropenia。
Themost 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（44%）miting（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%）。
HER2-Mutant Unresectable or Metastatic NSCLC（5.4mg/kg）
DESTINY-Lung02evaluated two dose levels（5.4mg/kg[n=101]and6.4mg/kg[n=50]）；however，only the results for the recommended dose of 5.4mg/kg intravenously every3weeks are described below due to increased toxicity observed with the higher dose in patients with NSCLC，including ILD/pneumonitis。
The safety of ENHERTU was evaluated in 101 patients with HER2-mutant unresectable or metastatic NSCLC who received ENHERTU5.4 mg/kg intravenously once every weeks until disease progression or unacceptable toxicity in DESTINY‑Lung02.Nineteen percent of patients wereexpod for>6。
Serious adverse reactions occurred in30%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.Fatalityoccurred in1patient withs。
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 in23%of patients.Adverse reactions which required dose interruption（>2%）included neutropenia and ILD/pneumonitis。Dose reductions due to an adverse reaction occurred in 11%of patients。
Themost 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 partate aminotransferase（35%），increased alanine aminotransferase（34%），fatigue（32%），constipation（31%），decreased appetite（30%），vomiting（26%），increased alkaline phosphatase（22%），and alopecia（21%）。
HER2-Positive Locally Advanced or Metastatic Gastric Cancer（6.4mg/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 every3 weeks or either inecotan（N=150）2biweekly or paclitaxel（N=7）80mg/m2weekly for3weeks.The median duration of treatment was4.6months（range:0.7to22.3）for patients who received ENHERTU。
Serious adverse reactions occurred in44%of patients receiving ENHERTU6.4mg/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%）。
ENHERTU was permanently discontinued in 15%of patients，of which ILD accounted for6%.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.Dose reductions occurred in32%of patients treated with ENHERTU.The most frequent adverreactions（>wiactions）were neutropenia，decreased appetite，fatigue，nausea，and febrile neutropenia。
Themost 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 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%）。
HER2-定位（IHC3+）Unresectable or Metastatic Solid Tumors
The safety of ENHERTU was evaluated in 347adult patients with unresectable or metatic HER2-positive（IHC3+）solid tumors who received ENHERTU5.4mg/kg intravenously once every3weeks in DESTINY-Breast01，DESTINY-PanTumor02，DESTINY-Lung01，and DESTINY-RandReduration was8.3months（range0.7to30.2）。
Serious adverse reactions occurred in34%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 cellulitis，and dyspnea.Fatalities due to adverse reactions occurred in6.3%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。
ENHERTU was permanently discontinued in 15%of patients，of which ILD/pneumonitis accounted for10%.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.Dose reductions occurred in27%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。
Themost 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 plate（51%）inotransferase（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 upperrespirofectory。
使用规范池
- 准备：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，orif a patient becomes pregnant within7months after the last dose of ENHERTU。
- Lactation:There are no data regarding the presence of ENHERTU in human milk，the effets on the breastfed child，or the effets 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 7months after the ladose。
- 重复使用条款：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 7months after the last dose。Males：Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4months after the last dose。Infertility:ENHERTU may impair male reproductive function and fertility。
- 人员使用：Safety and effectiveness of ENHERTU have not been established in pediatric patients。
- Geriatric User:Of the 1287 patients with HER2-positive or HER2-low breast cancer treated with ENHERTU5.4mg/kg，22%were≥65years and 3.8%were≥75years。Noverall differences in efficacy within clinical studies were observed between patients≥65years of age compared to younger patients.There was a higher incidence of Grade3-4adverse reactions observed in patients aged≥65years（59%）as compared to younger patients（49%）。Of the 101 patients with HER2-mutant unresectable or metastatic NSCLC treated with ENHERTU5.4mg/kg，40%were≥65years and 8%were≥75years。Noverall differences in efficacy or safety were observed between patients≥65years of age compared to younger patients.Of the 125 patients with HER2-positive locally advanced or metastic gastric or GEJ adenocarcinoma treated with ENHERTU6.4mg/kgin DESTINY-Gastric01，56%were≥65years and 14%were≥75years。Noverall differences in efficacy or safety were observed between patients≥65years of age compared to younger patients.Of the 192 patients with HER2-positive（IHC3+）unresectable or metatic solid tumors treated with ENHERTU5.4mg/kgin DESTINY-PanTumor02，DESTINY-Lung01，or DESTINY-CRC02,39%were65years or older and 9%were75years or older.Nooverall differences in efficicacy or safety were observed between patients≥65years of age compared to younger patients。
- Renal Impairment：Ahigher incidence of Grade1and2ILD/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 forpatients with severe renal impairment（CLcr<30mL/min）。
- 标题：In patients with moderate hepatic impairment，due to potentially increased exposure，closely monitor for increased toxicities related to the topoisommerase inhibitor，DXd.The recommended dosage of ENHERTU has not been established for patients with severe hepatic impairment（total bilubintim>3）。
To report SUSPECTED ADVERSE REACTIONS，contact Daiichi Sankyo，Inc.at1-877-437-7763or FDA at1-800-FDA-1088or fda.gov/medwatch。
喷射式通风管压缩信息单击功能区上，including Boxed WARNINGS，and通信指南。
About Daiichi Sankyo
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 than120 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.For more information，please visitwww.daiichisankyo.com。
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