The ENHERTU View

Listen to medical experts discuss the efficacy and safety of ENHERTU—demonstrated in DESTINYBreast-01 in patients with HER2+ unresectable or metastatic breast cancer who have received two or more prior anti-HER2 therapies in the metastatic setting—as well as their own experience treating these patients with ENHERTU.

    Chapter 1: The ENHERTU View Introduction

    Important Safety Information

    Indication

    ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

    This indication is approved under accelerated approval based on tumor 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.

    WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

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

    Contraindications

    None.

    Warnings and Precautions

    Interstitial Lung Disease / Pneumonitis

    Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, ILD occurred in 9% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients treated with ENHERTU. Median time to first onset was 4.1 months (range: 1.2 to 8.3).

    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 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. 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.

    Neutropenia

    Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 62% of patients. Sixteen percent had Grade 3 or 4 decrease in neutrophil count. Median time to first onset of decreased neutrophil count was 23 days (range: 6 to 547). Febrile neutropenia was reported in 1.7% of patients.

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

    Left 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-HER2 therapies, including ENHERTU. In the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, two cases (0.9%) of asymptomatic LVEF decrease were reported. 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.

    Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. 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. 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. 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.

    Embryo-Fetal 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 treatment and for at least 7 months following the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months after the last dose of ENHERTU.

    Additional Dose Modifications

    Thrombocytopenia

    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. Reduce dose by one level.

    Adverse Reactions

    The safety of ENHERTU was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY-Breast01 and Study DS8201-A-J101. ENHERTU was administered by intravenous infusion once every three weeks. The median duration of treatment was 7 months (range: 0.7 to 31).

    Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were interstitial lung disease, pneumonia, vomiting, nausea, cellulitis, hypokalemia, and intestinal obstruction. Fatalities due to adverse reactions occurred in 4.3% of patients including interstitial lung disease (2.6%), and the following events occurred in one patient each (0.4%): acute hepatic failure/acute kidney injury, general physical health deterioration, pneumonia, and hemorrhagic shock.

    ENHERTU was permanently discontinued in 9% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 33% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, thrombocytopenia, leukopenia, upper respiratory tract infection, fatigue, nausea, and ILD. Dose reductions occurred in 18% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, and neutropenia.

    The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (79%), white blood cell count decreased (70%), hemoglobin decreased (70%), neutrophil count decreased (62%), fatigue (59%), vomiting (47%), alopecia (46%), aspartate aminotransferase increased (41%), alanine aminotransferase increased (38%), platelet count decreased (37%), constipation (35%), decreased appetite (32%), anemia (31%), diarrhea (29%), hypokalemia (26%), and cough (20%).

    Use in Specific Populations

    • 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 following the last dose of ENHERTU.
    • 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.
    • 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 at least 7 months following the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months following the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.
    • Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
    • Geriatric Use: Of the 234 patients with HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, 26% were ≥65 years and 5% were ≥75 years. No overall differences in efficacy 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 (53%) as compared to younger patients (42%).
    • Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor.

    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.

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

    Chapter 1: The ENHERTU View Introduction

    ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

    This indication is approved under accelerated approval based on tumor 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.

    WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

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

    Please see Important Safety Information and Prescribing Information, including Boxed WARNINGS, on the website ENHERTUhcp.com/breast.

    Chapter 2: The Challenge to Treat

    So in most cases, when patients come in for the third-line treatment in metastatic HER2-positive breast cancer, they will have received T-DM1, and now the question is that third-line setting. Now, when we look at patients in that setting, they typically have lung metastases and/or liver metastases, making response rate extremely important because these patients may have symptoms from their disease.

    What we have seen in patients with metastatic HER2-positive breast cancer is that there’s a difference between the first-line, second, and third-line setting. So when we look at the progression-free survival in the first-line setting, we can see that progression-free survival being at around 18.5 months.

    In the second-line setting we see that progression-free survival decreasing; it’s 9.6 months. Then several trials in that third-line setting are showing us that the progression-free survival, it can be as low as 2.6 months.

    Similar to progression-free survival, which progressively shortens as patients get further into lines of therapy, response rate also drops.

    In terms of response rates, it drops from first line around 80%. If you go to second line, it’s anywhere between 22 to 49%. In the third line setting, anywhere between 10 to 31%, depending on which study you’re looking at. In my practice, I feel that it’s similar pattern. There’s increasing tumor burden, increased sites of metastases, and decreasing efficacy in terms of both response rate and progression-free survival.

    Now, one of the major issues with HER2-positive metastatic disease is the fact that 80% of our patients are going to have visceral metastases. Those metastases are going to be most commonly seen in the bones, the lung, the liver, as well as the CNS. Now, those patients that have visceral metastases are going to have worse prognosis.

    Chapter 3: ENHERTU Mechanism of Action

    ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

    This indication is approved under accelerated approval based on tumor 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.

    WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

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

    Please see Important Safety Information and Prescribing Information, including Boxed WARNINGS, on the website ENHERTUhcp.com/breast.

    As for the mechanism of action of ENHERTU, it’s a three part molecule antibody-drug conjugate. The antibody here is the same amino acid sequence as trastuzumab, that goes to the target, HER2, which is over expressed on HER2-positive cells.

    And then, is the payload, which is a topoisomerase 1 inhibitor, deruxtecan.

    It’s attached with a stable linker, which then is hydrolyzed by lysosomal enzymes within the cell, once it goes into the cell. So, there’s about 8:1 ratio of payload to antibody. Each antibody has eight molecules of the payload. And, as it gets into the cells and gets broken down, it can permeate to the surrounding cells, and also kills those cells, something known as the bystander effect.

    Chapter 4: DESTINY-Breast01 Trial

    ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

    This indication is approved under accelerated approval based on tumor 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.

    WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

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

    Please see Important Safety Information and Prescribing Information, including Boxed WARNINGS, on the website ENHERTUhcp.com/breast.

    Safety and efficacy of ENHERTU, were assessed in a large phase two trial, called DESTINY-Breast01. And, there were 184 patients in this study, that all had to have metastatic or locally advanced breast cancer, that had failed two lines of therapy, including one involving T-DM1. And, the performance status had to be 0 or 1. These patients could not have had active interstitial lung disease or previous history of interstitial lung disease. They also could not have active brain metastases. They were allowed to have treated brain metastases. And, they were all given ENHERTU at 5.4 mgs per kg, every three weeks, until unacceptable toxicity or progression.

    The primary endpoint was overall response rate, by RECIST 1.1. And, secondary endpoints included duration of response, disease control rate, overall survival, progression-free survival, and clinical benefit rate.

    When we look at the baseline characteristics of these women, we have 184 patients here. All female. Median age was 55. 55% were white. 53% were hormone receptor positive patients. And, performance status was zero for 55% of the patients. So overall, a relatively representative population of patients for this study.

    92% of patients that were included in the DESTINY-Breast01 trial had visceral metastases, and that included lung metastases, liver metastases, and 13% had stable brain metastases. Patients on DESTINY-Breast01 had to have T-DM1. They also had a large number of these patients receiving pertuzumab, as well as trastuzumab.

    It is important to remember that patients with stable brain metastases were included in the DESTINY-Breast01 clinical trial. 13% of patients on that trial had stable brain metastases and I personally use ENHERTU in this patient population.

    So the patients that we typically see with metastatic HER2-positive breast cancer that have progressed on second-line therapy are pretty similar to the ones that we have seen on DESTINY-Breast01. Their median age is going to be around 55, most of them are going to have a good performance status, and they will have multiple sites of visceral metastases, and in many of these cases, they will have both liver and lung disease.

    Chapter 5: Efficacy and Safety Data

    ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

    This indication is approved under accelerated approval based on tumor 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.

    WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

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

    Please see Important Safety Information and Prescribing Information, including Boxed WARNINGS, on the website ENHERTUhcp.com/breast.

    The primary endpoint for DESTINY-Breast01 was response rate. On that trial, the response rate was 60.3%. Most of the patients had partial responses, although a few patients had complete responses as well.

    The response was durable. There was a median duration of response of 14.8 months.

    Another secondary objective of DESTINY-Breast01 was progression-free survival. The median PFS was 16.4 months.

    When we try to evaluate clinical trials, especially in the metastatic setting and the third-plus-line setting, we’re looking at different endpoints. To me, response rate is extremely important because it really shows us how the tumor is shrinking. Patients in that third-line setting may have symptoms from their disease and this shrinkage may help improve those symptoms. So to me, response rate is a very clinically useful endpoint. But when we try to evaluate how effective our drugs are, we use median progression-free survival as one of those endpoints.

    So, when we look at this waterfall plot, which has every patient as a bar, and a zero is the baseline tumor size, so all the bars below the baseline show shrinkage in that particular patient, and all the bars above the line show growth.

    Four out of the 168 patients on this waterfall plot, actually showed growth of tumor, and one of those patients crossed the 20% growth line, which would constitute the definition of progression.

    Disease control rate was 97%. Clinical benefit rate, that was 76.1%. So, these numbers speak for themselves.

    The results from DESTINY-Breast01 are really compelling. When we look at a median duration of response that is close to 15 months, what we’re seeing is that this is durable response and therefore, again, helping our patients with an incurable disease.

    Every time we try to use a drug for a patient it is extremely important that we evaluate the benefit-risk ratio. The benefit from ENHERTU is clear in my mind. We have seen a remarkable response rate of over 60%; we have seen durable responses.

    The safety data from ENHERTU come from a pooled analysis from phase one and phase two clinical trials. When we’re looking at the most common adverse reactions, those included GI side effects such as nausea, vomiting, constipation, diarrhea...some fatigue, alopecia, decreased appetite, and anemia. Most of these adverse reactions were grade one and two.

    Most common grade three and four adverse reactions, occurring in at least 2% of patients, were fatigue, nausea, ILD, vomiting, and anemia.

    So when we look at patients who had to discontinue, interrupt or dose reduce the treatment, there were 9% discontinuations, 33% dose interruptions and 18% dose reductions.

    And the most common—which would be 20% or greater adverse reactions, including laboratory abnormalities—were nausea, white blood cell count decreased, hemoglobin decreased, neutrophil count decreased, fatigue, vomiting, alopecia, AST and ALT elevations, platelet count decreased, constipation, decreased appetite, anemia, diarrhea, hypokalemia and cough.

    In terms of managing adverse events, it’s pretty clear that we should use prophylactic antiemetics with this drug. And I generally use 5-HT3 antagonist along with dexamethasone. Some may add additional medication, that also depends on patient individually. And I always order prochlorperazine and ondansetron to be taken at home on as needed basis. So then patients are covered.

    I haven’t had to use much stronger nausea control with this compound. In the trial, it was left to the discretion of the investigator or institutional guidelines. In terms of diarrhea, there’s no prophylaxis necessary. However, patients who have diarrhea use a Loperamide as per standard guidelines. And in terms of other side effects, patients might experience lack of appetite. We can use drugs to stimulate appetite.

    So when I look at data from ENHERTU—I know that the patient population that we treat here, which is third line and beyond—has widely metastatic disease. 80% of these patients have visceral disease. Some may have rapid tempo of disease. And cytotoxic chemotherapy in general has the side effects of alopecia, nausea, vomiting, fatigue, myelosuppression, mucositis, diarrhea. So considering those other cytotoxic side effects that we see—vis-a-vis what we saw in this patient population.

    At the end of the day, it’s a joint decision. You sit down with the patient, discuss all the options, pros and cons, their preferences and then you will arrive at a decision. And in that realm, I found it easy to prescribe this compound in this particular setting.

    Chapter 6: Monitoring for Interstitial Lung Disease/Pneumonitis

    ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

    This indication is approved under accelerated approval based on tumor 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.

    WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

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

    Please see Important Safety Information and Prescribing Information, including Boxed WARNINGS, on the website ENHERTUhcp.com/breast.

    One of the toxicities that we have to take into account is interstitial lung disease. This is something that we all have to be very aware of, make our patients aware of, ask the right questions, and try to identify it early—so that we can either hold ENHERTU, and treat our patients, or permanently discontinue ENHERTU. It’s important that we pay attention to ILD so that we can identify symptoms as early as we possibly can.

    Interstitial lung disease and ILD pneumonitis, including grade 5, have been reported with ENHERTU. Most of the cases were grade 1-2, 16 out of the 22 patients. And, these 22 patients amount to 9% of the patient population. Grade 5 fatal events occurred in 2.6%, which was six patients. And, median time to first onset, was 4.1 months. Range being 1.2 to 8.3 Months. We really have to talk to our patients about this potential toxicity with ENHERTU.

    So, for asymptomatic ILD, which would often be discovered on imaging studies that are done for response assessment, we discontinue the treatment and start treatment with 0.5 mg per kg of prednisolone equivalent. If symptoms resolved within 28 days, we can maintain the dose. If it takes longer, we go down by one dose level.

    However, for symptomatic ILD, which would be Grade 2 or greater, we permanently discontinue the drug, and the treatment with steroids is 1 mg per kg equivalent of prednisolone, given for 14 days, and then we start the slow taper over the next four to six weeks. And again, we permanently discontinue the drug in those cases of Grade 2 or greater, which is symptomatic ILD.

    So, my advice to peers is to be very vigilant. It starts with patient education. We educate the patient to report these symptoms immediately. Not wait until after the weekend to call the office during the office hours. We actually have our nurses call the patients once a week to check on them and ask basic questions about cough, dyspnea, increase inhaler use, fever, any other new symptoms. And, I advise my colleagues that it’s a manageable toxicity, provided it’s diagnosed early.

    Chapter 7: Dosing & Administration

    ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

    This indication is approved under accelerated approval based on tumor 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.

    WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

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

    Please see Important Safety Information and Prescribing Information, including Boxed WARNINGS, on the website ENHERTUhcp.com/breast.

    ENHERTU is dose based on body weight. And, the dose is 5.4 mgs per kg, given intravenously every three weeks. The first infusion is given over 90 minutes. And, if all goes well, subsequent infusions can be given over 30 minutes each.

    So, dose adjustments may be necessary based on adverse reactions on how the patient tolerates the drug. The first dose reduction would be to go down from 5.4 mgs per kg to 4.4 mgs per kg. And, the further dose reduction, if necessary, would be to 3.2 mgs per kg. If you need any reduction beyond that, then it’s advisable to discontinue the drug.

    Further dose reduction below that is not recommended. If some dose delay occurs for whatever reason, you don’t have to wait until the next planned dose. We can give the next dose immediately. However, subsequent interval needs to be adjusted to remain every three weeks. And, we give the next dose at the dose and rate that patient tolerated previously.

    Chapter 8: The Appropriate Patients for Treatment

    ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

    This indication is approved under accelerated approval based on tumor 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.

    WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

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

    Please see Important Safety Information and Prescribing Information, including Boxed WARNINGS, on the website ENHERTUhcp.com/breast.

    When I think of my patients who are beyond two lines of therapy and I’m discussing their next options. Most often, many of them have comorbidities. They have multiple sites of metastatic disease. About 80% of them may have visceral metastases. And you have to look at the totality of options and the historic experience that we have had in this space and look at the data from DESTINY-Breast01...

    And when I go by the NCCN guidelines which I tend to follow. Then those with visceral disease, which is the vast majority of these patients, ENHERTU is the preferred option.

    The NCCN guidelines have gone through several permutations in the HER2-positive setting, especially with several drugs being approved.

    As far as ENHERTU, it is now a option as far as the NCCN guidelines are concerned in the third-line setting, in patients with visceral metastases. But when I look at these guidelines, I mostly evaluate the clinical trial data.

    We have patients on the DESTINY-Breast01 trial that also had stable brain metastases included, and so when I try to decide who the right patient is for ENHERTU, I look at a patient that will have some visceral metastases, may have stable brain metastases as well, and I’m looking for a response.

    Ready to learn more about ENHERTU?