AstraZeneca ASCO 2021 Data Support Ambition to Revolutionize Cancer Outcomes by Treating Earlier and Transforming the Patient Experience

LYNPARZA is the first targeted medicine to show clinical benefit in the adjuvant setting for patients with germline BRCA-mutated high-risk HER2-negative early breast cancer

CALQUENCE shows sustained four-year clinical benefit in 1st-line chronic lymphocytic leukemia and lower atrial fibrillation rates in previously treated patients vs. ibrutinib

IMFINZI five-year data represent longest-ever survival reported in a Phase III immunotherapy trial in unresectable Stage III lung cancer

AstraZeneca will present new data underscoring its ambition to redefine cancer care at the American Society of Clinical Oncology (ASCO) Annual Meeting, June 4 to 8, 2021.

More than 100 abstracts will feature 21 approved and potential new medicines across the Company’s industry-leading oncology portfolio, with four abstracts selected as late-breakers, 12 oral presentations and one plenary presentation.

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “Our data at ASCO this year show our unwavering resolve to revolutionize cancer care and strengthen our leading portfolio in lung and breast cancers as well as hematology. New results for LYNPARZA^® (olaparib) and IMFINZI^® (durvalumab) continue to validate our strategy of treating cancer early in settings with curative intent, and data for CALQUENCE deliver on our commitment to improve the patient experience by demonstrating efficacy with safe, tolerable medicines.”

Cristian Massacesi, Senior Vice President, Head of Late-Stage Development, Oncology R&D said: “Over the past few years, the outlook for breast cancer patients with BRCA mutations has radically changed, and the OlympiA data at ASCO will represent another critical step forward. We have an opportunity to fundamentally change the prognosis for women with high-risk early disease and usher in a potential new standard of care in the adjuvant setting. Additionally, promising data in triple-negative breast cancer will challenge current treatment expectations and bring hope for new approaches in this aggressive form of the disease.”

Redefining survival by treating cancer earlier

A plenary presentation of results from the OlympiA Phase III trial in early breast cancer will highlight the impact of LYNPARZA on the risk of disease recurrence versus placebo in the adjuvant treatment of patients with germline BRCA-mutated (gBRCAm) high-risk human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. LYNPARZA is the first PARP inhibitor to demonstrate clinical benefit as an adjuvant treatment in early breast cancer. In February 2021, the trial’s Independent Data Monitoring Committee recommended moving to early primary analysis based on a planned interim analysis showing a sustainable and clinically relevant treatment effect in the primary endpoint of invasive disease-free survival.

Five-year overall survival data from the PACIFIC Phase III trial will continue to support the unprecedented and sustained survival benefits of IMFINZI for patients with unresectable, Stage III non-small cell lung cancer (NSCLC) who have not progressed following concurrent chemoradiation therapy. These data represent the longest-ever survival reported in a Phase III trial of immunotherapy in this treatment setting.

Additionally, an oral presentation of Phase II data from the externally sponsored GeparNuevo trial conducted by the German Breast Group will show initial potential of IMFINZI to improve outcomes in patients with early triple-negative breast cancer (TNBC) when added to standard neoadjuvant chemotherapy.

Transforming the patient experience

Four-year follow-up data from the ELEVATE-TN trial will confirm the sustained clinical benefit of either CALQUENCE^® (acalabrutinib) monotherapy or CALQUENCE in combination with obinutuzumab, providing flexibility to tailor treatment for adults with treatment-naïve chronic lymphocytic leukemia (CLL).

In addition, an oral presentation of detailed results from the ELEVATE-RR Phase III trial will demonstrate significantly lower atrial fibrillation, fewer cardiac events and fewer discontinuations with CALQUENCE versus ibrutinib in adults with previously treated CLL at high risk for progression. ELEVATE-RR is the first head-to-head Phase III trial of two Bruton’s tyrosine kinase inhibitors (TKIs) in CLL, confirming the favorable benefit-risk profile of CALQUENCE for patients with CLL.

Updated data from DESTINY-Gastric01 and DESTINY-CRC01 will further support the potential role of ENHERTU (fam-trastuzumab deruxtecan-nxki) across HER2-targetable cancers. Additionally, data from a subgroup analysis of previously treated HER2-positive breast cancer patients with brain metastases in the DESTINY-Breast01 trial will reinforce the commitment to understanding the potential benefit of ENHERTU in hard-to-treat patient populations.

Initial results will be shared from the BEGONIA Phase Ib/II trial testing IMFINZI combinations in metastatic TNBC, including with ENHERTU. Also, data will be shared from a Phase II trial with ceralasertib, an ataxia telangiectasia and rad3-related (ATR) kinase inhibitor, in combination with IMFINZI showing that this combination demonstrated promising anti-tumor activity in melanoma patients for whom prior anti-PD1 treatment had failed.

Additional evidence will underscore the need for improved central nervous system control and the role of next-generation TKIs such as TAGRISSO^® (osimertinib) in the treatment of advanced epidermal growth factor (EGFR)-mutated NSCLC, as shown in the REFLECT retrospective real-world analysis of first- and second-generation TKIs.

Advancing an industry-leading clinical development program

In all, AstraZeneca will share 18 posters at ASCO describing trials-in-progress exploring novel medicines and combinations across multiple types and stages of cancer. These posters include:

• Datopotamab deruxtecan (Dato-DXd) - the TROPION-Lung01 Phase III trial testing datopotamab deruxtecan in patients with previously treated metastatic NSCLC, and the BEGONIA trial testing IMFINZIin combination with datopotamab deruxtecan in metastatic TNBC
• ENHERTU - trials testing ENHERTU alone or in various combinations, including: DESTINY-Breast07, DESTINY-PanTumor01, and DESTINY-CRC02
• IMFINZI - the MATTERHORN Phase III trial of neoadjuvant-adjuvant IMFINZI and chemotherapy in resectable gastric and gastroesophageal junction cancer, and the BEGONIA Phase I/II trial testing IMFINZI in novel combinations for 1st-line treatment of patients with TNBC, including with ENHERTU and datopotamab deruxtecan.
• CALQUENCE - the ESCALADE Phase III trial of CALQUENCE in combination with standard chemotherapy for patients age 65 and younger newly diagnosed with diffuse large B-cell lymphoma, the most common type of non-Hodgkin lymphoma
• Camizestrant (AZD9833) - the SERENA-4 Phase III trial comparing camizestrant, a next-generation oral selective estrogen receptor degrader (SERD), plus palbociclib, versus anastrozole plus palbociclib, in patients with estrogen receptor-positive, HER2-negative advanced breast cancer who have not previously received systemic treatment for advanced disease
• Adavosertib - the ADAGIO Phase II multicenter trial of the WEE1 inhibitor adavosertib as a treatment for recurrent or persistent uterine serous carcinoma, a highly aggressive form of endometrial cancer

Collaboration in the scientific community is critical to improving outcomes for patients. LYNPARZA is developed and commercialized in collaboration with Merck & Co., Inc. AstraZeneca is collaborating with Daiichi Sankyo Company, Limited (Daiichi Sankyo) to develop and commercialize ENHERTU and datopotamab deruxtecan globally.

Key AstraZeneca presentations during the 2021 ASCO Annual Meeting¹

SELECT SAFETY INFORMATION for LYNPARZA® (olaparib) tablets

LYNPARZA is associated with serious, potentially fatal risks, including myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), pneumonitis. Additionally, serious, potentially fatal risk of venous thromboembolic events has been reported with LYNPARZA in mCRPC. LYNPARZA can also cause fetal harm.

U.S. FDA-APPROVED INDICATIONS

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

First-Line Maintenance BRCAm Advanced Ovarian Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance HRD Positive Advanced Ovarian Cancer in Combination with Bevacizumab

In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:

• a deleterious or suspected deleterious BRCA mutation, and/or
• genomic instability

Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Maintenance Recurrent Ovarian Cancer

For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.

Advanced gBRCAm Ovarian Cancer

For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

gBRCAm, HER2-Negative Metastatic Breast Cancer

For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer

For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Please click here for complete Prescribing Information, including Patient Information (Medication Guide).

SELECT SAFETY INFORMATION FOR IMFINZI® (durvalumab)

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis and renal dysfunction, and solid organ transplant rejection. IMFINZI can cause severe or life-threatening infusion-related reactions. Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody.

Advise women not to become pregnant or breastfeed during treatment with IMFINZI and for at least 3 months after the last dose.

In the PACIFIC trial, the most frequent serious adverse reactions reported in at least 2% of patients were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%).

The most common adverse reactions were cough, fatigue, pneumonitis or radiation pneumonitis, upper respiratory tract infections, dyspnea, and rash.

The safety and effectiveness of IMFINZI have not been established in pediatric patients.

Please click here for complete Prescribing Information, including Patient Information.

SELECT SAFETY INFORMATION FOR CALQUENCE® (acalabrutinib)

INDICATION AND USAGE

CALQUENCE is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

SELECT SAFETY INFORMATION

Serious adverse events, including fatal events, have occurred with CALQUENCE, including serious and opportunistic infections, hemorrhage, cytopenias, second primary malignancies, and atrial fibrillation and flutter. The most common adverse reactions (≥ 30%) of any grade in patients with CLL were anemia, neutropenia, thrombocytopenia, headache, upper respiratory tract infection, and diarrhea.

Please see full Prescribing Information including Patient Information.

SELECT SAFETY INFORMATION FOR TAGRISSO® (osimertinib)

• There are no contraindications for TAGRISSO
• TAGRISSO is associated with several serious and sometimes fatal adverse reactions, including interstitial lung disease/pneumonitis, QTc interval prolongation, cardiomyopathy, keratitis, erythema multiforme and Stevens-Johnson syndrome, and embryo-fetal toxicity
• The most common adverse reactions (≥20%) were diarrhea, rash, dry skin, nail toxicity, stomatitis, fatigue, and decreased appetite

U.S. FDA-APPROVED INDICATIONS

• TAGRISSO is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
• TAGRISSO is indicated for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy

Please see complete Prescribing Information, including Patient Information.

IMPORTANT SAFETY INFORMATION FOR ENHERTU® (fam-trastuzumab deruxtecan-nxki)

Indications

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.

• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.

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. 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.

Metastatic Breast Cancer

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).

Locally Advanced or Metastatic Gastric Cancer

In DESTINY-Gastric01, of the 125 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 21.0).

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 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.

Metastatic Breast Cancer

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.

Locally Advanced or Metastatic Gastric Cancer

In DESTINY-Gastric01, of the 125 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. 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. In DESTINY-Gastric01, of the 125 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. 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

Metastatic Breast Cancer

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%).

Locally Advanced or Metastatic Gastric Cancer

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 once every three weeks or either irinotecan (N=55) 150 mg/m² biweekly or paclitaxel (N=7) 80 mg/m² weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) in the ENHERTU group and 2.8 months (range: 0.5 to 13.1) in the irinotecan/paclitaxel group.

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 hypokalemia. 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 hemoglobin decreased (75%), white blood cell count decreased (74%), neutrophil count decreased (72%), lymphocyte count decreased (70%), platelet count decreased (68%), nausea (63%), decreased appetite (60%), anemia (58%), aspartate aminotransferase increased (58%), fatigue (55%), blood alkaline phosphatase increased (54%), alanine aminotransferase increased (47%), diarrhea (32%), hypokalemia (30%), vomiting (26%), constipation (24%), blood bilirubin increased (24%), pyrexia (24%), and alopecia (22%).

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%). Of the 125 patients with locally advanced or metastatic HER2‑positive 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.
• 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.

NOTES TO EDITORS

About 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, primarily for the treatment of diseases in three therapy areas – Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow the Company on Twitter @AstraZenecaUS.

US-54022 Last Updated 5/21

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