HER2-Low Breast Carcinoma

ENHERTU is indicated for patients with unresectable or metastatic NSCLC with activating HER2 mutations who have previously undergone systemic therapy. Credit: Nemes Laszlo/Shutterstock. Daiichi Sankyo and AstraZeneca ‘s ENHERTU has been conditionally approved by China’s National Medical Products Administration (NMPA) as a single agent for adult patients with a specific type of non-small cell lung cancer (NSCLC). Free Whitepaper Intensified Biomanufacturing of monoclonal antibodies Using an intensified fed-batch process is a viable alternative for higher protein production at a large scale without expanding the current manufacturing footprint. Syngene’s expertise in the field is covered in this white paper. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. Go deeper with GlobalData Reports LOA and PTSR Model - DF-9001 in Non-Small Cell Lung Cancer Reports LOA and PTSR Model - Eniluracil in Metastatic Breast Cancer Data Insights The gold standard of business intelligence. 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Our services are intended for corporate subscribers and you warrant that the email address submitted is your corporate email address. The therapy is indicated for patients with unresectable or metastatic NSCLC with activating HER2 mutations who have previously undergone systemic therapy. It marks the fourth approval in China for ENHERTU, which has been authorised for use in three different tumour types: HER2-low metastatic breast cancer, and HER2-positive advanced or metastatic gastric cancer . ENHERTU, a HER2-directed antibody-drug conjugate (ADC), was discovered by Daiichi Sankyo and is being developed and commercialised in collaboration with AstraZeneca. The conditional approval is based on the outcomes of the DESTINY-Lung02 and DESTINY-Lung05 Phase II studies. See Also: Evergreen Theragnostics Radiopharmaceutical Manufacturing Facility, New Jersey, US Merck Biotech Development Center, Corsier-sur-Vevey, Switzerland In the DESTINY-Lung02 trial, ENHERTU achieved the primary endpoint with a confirmed overall response rate (ORR) of 49%, 49 partial responses (PRs) and one complete response (CR), as evaluated by blinded independent central review (BICR). The DESTINY-Lung05 trial demonstrated a confirmed ORR of 58.3%, one CR and 41 PRs, as determined by an ICR. AstraZeneca oncology business unit executive vice-president Dave Fredrickson stated: “This approval of ENHERTU represents the first HER2 directed therapy approved in China for the treatment of HER2 mutant metastatic non-small cell lung cancer, marking an important step forward in how the disease can be treated. “It also reinforces the importance of testing for predictive biomarkers, including HER2 mutations in lung cancer at the time of diagnosis, to ensure patients can receive the most appropriate treatment for their specific disease.” The full approval of ENHERTU for this indication in China will depend on the clinical benefits observed in the confirmatory trial. Enhertu was approved in the US as the first tumour-agnostic HER2-directed therapy in April 2024 for previously treated patients with metastatic HER2-positive solid tumours. 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Based on DESTINY-Breast06 Phase III trial which demonstrated a statistically significant and clinically meaningful progression-free survival benefit for ENHERTU If approved, AstraZeneca and Daiichi Sankyo’s ENHERTU will be the first HER2 directed therapy and ADC for patients prior to receiving chemotherapy for metastatic breast cancer ENHERTU also granted Breakthrough Therapy Designation in the US for this patient population WILMINGTON, DE, USA I October 01, 2024 I AstraZeneca and Daiichi Sankyo’s supplemental Biologics License Application (sBLA) for ENHERTU ® (fam-trastuzumab deruxtecan-nxki) has been accepted and granted Priority Review in the US for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer who have received at least one endocrine therapy in the metastatic setting based on positive results from the DESTINY-Breast06 Phase III trial which compared ENHERTU to chemotherapy. The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is anticipated during the first quarter of 2025. ENHERTUwas also recently granted Breakthrough Therapy Designation (BTD) by the FDA in this setting. BTD accelerates the development and regulatory review of potential new medicines intended to treat a serious condition and address a significant unmet medical need. HR-positive, HER2-negative is the most common breast cancer subtype, accounting for approximately 70% of all breast cancers. 1 Despite being classified as HER2-negative, many of these tumors still carry some level of HER2 expression. 2 It is estimated that up to 85-90% of tumors historically classified as HR-positive, HER2-negative may be HER2-low or HER2-ultralow. 3,4 Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “While endocrine therapies are widely used in the initial treatment of HR-positive metastatic breast cancer, most patients see limited benefit with additional lines of treatment, and subsequent chemotherapy is often associated with poor response rates and outcomes. The results from DESTINY-Breast06 show thatENHERTUhas the potential to evolve the current HR-positive treatment landscape and become the first targeted treatment for patients with HER2-low or HER2-ultralow expression following endocrine therapy.” Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “This Priority Review highlights the potential to expand the existing indication of ENHERTU in HER2-low metastatic breast cancer to include use in an earlier disease setting as well as in a broader patient population that includes HER2-ultralow. We look forward to working closely with the FDA with the goal of bringing ENHERTU to more patients as quickly as possible.” The sBLA is based on data from the DESTINY-Breast06 Phase III trial presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and recently published in The New England Journal of Medicine . In the trial, ENHERTU reduced the risk of disease progression or death by 37% by blinded independent central review (BICR) versus chemotherapy (hazard ratio [HR] 0.63; 95% confidence interval [CI]: 0.53-0.75; p< 0.0001) in the overall trial population. Median PFS was 13.2 months with ENHERTUcompared to 8.1 months with chemotherapy. Results were consistent between patients with HER2-low expression and HER2-ultralow expression. In the primary endpoint analysis of patients with HER2-low expression, ENHERTU showed a median PFS of 13.2 months compared to 8.1 months for chemotherapy (HR 0.62; 95% CI 0.51-0.74; p<0.0001). In a prespecified exploratory analysis of patients with HER2-ultralow expression, ENHERTU showed a median PFS of 13.2 months versus 8.3 months, respectively (HR 0.78; 95% CI 0.50-1.21). The safety profile of ENHERTU in DESTINY-Breast06 was consistent with previous clinical trials of ENHERTUin breast cancer with no new safety concerns identified. ENHERTU is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo. ENHERTUis already approved in more than 65 countries, including the US, for patients with HER2-low metastatic 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. Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Please see accompanying full Prescribing Information , including Boxed WARNINGS, and Medication Guide. Notes Breast cancer and HER2 expression Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide. 5 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally. 5 While survival rates are high for those diagnosed with early breast cancer, only approximately 30% of patients who are diagnosed with or who progress to metastatic disease are expected to live five years after their diagnosis. 1 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including breast cancer. 6 Patients with high levels of HER2 expression (IHC 3+ or 2+/ISH+) are classified as HER2-positive and treated with HER2-directed therapies, representing approximately 15-20% of all breast cancers. 7 Historically, tumors that were not classified as HER2-positive were classified as HER2-negative. 2 HR-positive, HER2-negative is the most common breast cancer subtype, accounting for approximately 70% of all breast cancers. 1 Despite being classified as HER2-negative, many of these tumors still carry some level of HER2 expression. 2 It is estimated that 60-65% of HR-positive, HER2-negative breast cancers are HER2-low and an additional 25% may be HER2-ultralow. 3,4 Endocrine therapies are widely used in the early lines of treatment for HR-positive metastatic breast cancer; however, after two lines of treatment, further efficacy from endocrine therapy is often limited. 8 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes. 8-11 Prior to the approval of ENHERTU in HER2-low metastatic breast cancer post chemotherapy based on the DESTINY-Breast04 trial, there were no targeted therapies approved specifically for patients with HER2-low expression. There are no targeted therapies specifically approved for patients with HER2-low expression prior to chemotherapy or for patients with HER2-ultralow expression. 12 DESTINY-Breast06 DESTINY-Breast06 is a global, randomized, open-label, Phase III trial evaluating the efficacy and safety ofENHERTU (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 2+/ISH-) or HER2-ultralow (defined as IHC 0 with membrane staining) advanced or metastatic breast cancer. 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 were also 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 1st-line treatment or received endocrine therapy as an adjuvant treatment and experienced disease recurrence within 24 months. HER2 status in the trial was confirmed by central laboratory and was performed on an archival tumor sample obtained at the time of initial metastatic diagnosis or later. If archival tissue was not available, a fresh tissue sample was required. 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 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. DESTINY-Breast06 enrolled 866 patients (n=713 for HER2-low and n=153 for HER2-ultralow) randomized at multiple sites in Asia, Europe, Australia, North America and South America. For more information about the trial, visit ClinicalTrials.gov . ENHERTU (fam-trastuzumab deruxtecan-nxki) ENHERTU (fam-trastuzumab deruxtecan-nxki) is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTUis 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 than 65 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [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 (5.4mg/kg) is approved in more than 65 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 (5.4mg/kg) is approved in more than 45 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 and/or DESTINY-Lung05 trials. Continued approval in the US 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 than 45 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 , DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Full approval in China for this indication will depend on whether a randomized controlled confirmatory clinical trial can demonstrate clinical benefit in this population. ENHERTU (5.4mg/kg) is approved in the US 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. Continued approval for this indication in the US may be contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU development program 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 anti-cancer treatments, such as immunotherapy, also are underway. Daiichi Sankyo collaboration AstraZeneca and Daiichi Sankyo 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. AstraZeneca in breast cancer Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death. AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumor environment. With ENHERTU (fam-trastuzumab deruxtecan-nxki), a HER2-directed antibody drug conjugate (ADC), AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings. In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines goserelin and aims to reshape the HR-positive space with first-in-class AKT inhibitor, capivasertib, and next-generation SERD and potential new medicine camizestrant. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting. PARP inhibitor olaparib is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research olaparib in these settings and to explore its potential in earlier disease. To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy durvalumab, capivasertib in combination with chemotherapy, and durvalumab in combination with other oncology medicines, including olaparib and ENHERTU. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca . References SOURCE: AstraZeneca

WILMINGTON, Del.--( BUSINESS WIRE )--High-level results from the TROPION-Breast01 Phase III trial of datopotamab deruxtecan (Dato-DXd) compared to investigator’s choice of chemotherapy, which previously met the dual primary endpoint of progression-free survival (PFS), did not achieve statistical significance in the final overall survival (OS) analysis in patients with inoperable or metastatic hormone receptor (HR)-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously treated with endocrine-based therapy and at least one systemic therapy. This analysis follows positive PFS results presented at the 2023 European Society for Medical Oncology Congress which showed datopotamab deruxtecan demonstrated a statistically significant and clinically meaningful improvement in PFS. An improvement in patient-reported outcomes was also seen. 1 The PFS data and additional results for key secondary endpoints were published this month in the Journal of Clinical Oncology. The safety profile of datopotamab deruxtecan was consistent with that observed in the previous analysis including lower rates of Grade 3 or higher treatment-related adverse events compared to chemotherapy, and no new safety concerns identified. All grade interstitial lung disease (ILD) rates remained low with no new Grade 3 or higher ILD events observed. With multiple antibody drug conjugates (ADCs) approved during the course of the trial, including ENHERTU ® (fam-trastuzumab deruxtecan-nxki), subsequent treatment following patients’ disease progression or treatment discontinuation is likely to have affected survival results. Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “ The metastatic HR-positive breast cancer treatment landscape has advanced remarkably in the last several years to benefit patients. Based on the TROPION-Breast01 results, there is evidence of the clinical value of datopotamab deruxtecan in this setting. We will continue discussions with regulatory authorities and apply insights from these results to our clinical development program for datopotamab deruxtecan in breast cancer.” Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “ Datopotamab deruxtecan has previously shown a statistically significant progression-free survival benefit in TROPION-Breast01, a result supported by multiple meaningful secondary measures including patient-reported outcomes. We are proud to have brought forth a new standard of care for patients with metastatic breast cancer with ENHERTU and we remain committed to making datopotamab deruxtecan another potential option for patients who can benefit.” Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd ADC discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo. The data will be presented at a forthcoming medical meeting and shared with regulatory authorities currently reviewing applications for this indication. In addition to TROPION-Breast01, AstraZeneca and Daiichi Sankyo are evaluating datopotamab deruxtecan alone and with immunotherapy as treatment for patients with triple-negative or HR-low, HER2-negative breast cancers in the TROPION-Breast02 , TROPION-Breast03 , TROPION-Breast04 and TROPION-Breast05 Phase III trials. IMPORTANT SAFETY INFORMATION Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Unresectable or metastatic HER2-positive (IHC 3+ or ISH 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 (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 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. 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. 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 Unresectable or metastatic HER2-positive (IHC3+) solid tumors who have received prior systemic treatment and have no satisfactory 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. 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. 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. 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. HER2-Positive or HER2-Low Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including 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. HER2-Positive Locally Advanced or Metastatic Gastric Cancer (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). 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 Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 10 9 /L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 10 9 /L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by one level. For febrile neutropenia (ANC <1.0 x 10 9 /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. HER2-Positive or HER2-Low Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including 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). Febrile neutropenia was reported in 1% of patients. HER2-Positive Locally Advanced or Metastatic Gastric Cancer (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). Febrile neutropenia was reported in 4.8% of patients. 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. 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 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. 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-Positive or HER2-Low Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including 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. HER2-Positive Locally Advanced or Metastatic Gastric Cancer (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. 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 7 months after the last dose of ENHERTU. 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. Additional Dose Modifications Thrombocytopenia For Grade 3 thrombocytopenia (platelets <50 to 25 x 10 9 /L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 10 9 /L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by one level. Adverse Reactions HER2-Positive and HER2-Low Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including 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. 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%). HER2-Positive Metastatic Breast Cancer 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). 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). 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. 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. 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%). HER2-Low Metastatic Breast Cancer 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. 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). 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. 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. 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%). HER2-Mutant Unresectable or Metastatic 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. 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. 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%). 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. Adverse reactions which required dose interruption (>2%) included neutropenia and ILD/pneumonitis. Dose reductions due to an adverse reaction occurred in 11% of patients. 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%). HER2-Positive Locally Advanced or Metastatic Gastric Cancer (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/m 2 biweekly or paclitaxel (N=7) 80 mg/m 2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) for patients who received ENHERTU. 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%). 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. 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. 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%). HER2-Positive (IHC3+) Unresectable or Metastatic Solid Tumors 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). 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. 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. 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. 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. 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%). 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 after 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 7 months after the last dose. 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. Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients. 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%). 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. 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. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. 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). 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). 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 . Notes HR-positive breast cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide. 2 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally. 2 While survival rates are high for those diagnosed with early breast cancer, less than 35% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis. 3 Approximately 70% of diagnosed cases are considered what has been historically called HR-positive, HER2-negative breast cancer (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-). 3 Endocrine therapies are widely given consecutively in the early lines of treatment for HR-positive metastatic breast cancer; however, after two lines of treatment, further efficacy from endocrine therapy is often limited. 4 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes. 4-7 TROP2 is a protein broadly expressed in HR-positive, HER2-negative breast cancer and is associated with increased tumor progression and poor survival. 8,9 TROPION-Breast01 ​TROPION-Breast01 is a global, randomized, multicenter, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0mg/kg) versus investigator’s choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in adult patients with unresectable or metastatic HR-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have progressed on and are not suitable for endocrine therapy per investigator assessment and have received at least one additional systemic therapy for unresectable or metastatic disease. Following disease progression or discontinuation of datopotamab deruxtecan or chemotherapy, patients had the option to receive subsequent treatment at the discretion of their physician. Crossover between trial arms was not permitted. The dual primary endpoints of TROPION-Breast01 are PFS as assessed by blinded independent central review and OS. Key secondary endpoints include objective response rate, duration of response, investigator-assessed PFS, disease control rate, time to first subsequent therapy and safety. TROPION-Breast01 enrolled more than 700 patients in Africa, Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov . Datopotamab deruxtecan (Dato-DXd) ​Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer (TNBC) and HR-positive, HER2-negative breast cancer. The program includes seven Phase III trials in lung cancer and five Phase III trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings. Daiichi Sankyo collaboration AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialize fam-trastuzumab deruxtecan-nxki 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 fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan. AstraZeneca in breast cancer ​Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death. AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumor environment. With fam-trastuzumab deruxtecan-nxki, a HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings. In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines goserelin and aims to reshape the HR-positive space with first-in-class AKT inhibitor, capivasertib, and next-generation SERD and potential new medicine camizestrant. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting. PARP inhibitor olaparib is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research olaparib in these settings and to explore its potential in earlier disease. To bring much-needed treatment options to patients with TNBC, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy durvalumab, capivasertib in combination with chemotherapy, and durvalumab in combination with other oncology medicines, including olaparib and fam-trastuzumab deruxtecan-nxki. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. About AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca . References Pernas S, et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer: Patient-reported outcomes (PROs) from the TROPION-Breast01 study. Presented at: ASCO Congress 2024; 31 May - 4 June, 2024; Chicago, IL. Abstract 1006. 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