Purpura, Schoenlein-Henoch

Decision based on FLAURA2 Phase III trial results which extended median progression-free survival by nearly 9 months versus standard of care WILMINGTON, Del.--(BUSINESS WIRE)-- AstraZeneca Pharmaceuticals LP’s supplemental New Drug Application (sNDA) for TAGRISSO® (osimertinib) in combination with chemotherapy has been accepted and granted Priority Review in the US for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). 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.1 The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is anticipated during the first quarter of 2024. Each year, there are an estimated 2.2 million people diagnosed with lung cancer globally with 80-85% of patients diagnosed with NSCLC, the most common form of lung cancer.2-4 Approximately 70% of people are diagnosed with advanced NSCLC.5 Additionally, about 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.6-8 Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The FLAURA2 results reinforce TAGRISSO as a backbone of standard of care in 1st-line EGFR-mutated non-small cell lung cancer, providing patients with an additional nine months of median progression-free survival when combined with chemotherapy. This option is particularly important for patients with a poorer prognosis such as those with brain metastasis. We look forward to working with the FDA on an accelerated timeline to bring this treatment regimen to patients as quickly as possible.” The sNDA is based on data from the FLAURA2 Phase III trial presented in a Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer (WCLC). In the trial, TAGRISSO in combination with chemotherapy reduced the risk of disease progression or death by 38% compared to TAGRISSO monotherapy, the 1st-line global standard of care (based on a hazard ratio [HR] of 0.62; 95% confidence interval [CI] 0.49-0.79; p<0.0001). By investigator assessment, the combination extended median PFS by 8.8 months versus TAGRISSO alone. PFS results from blinded independent central review were consistent, showing TAGRISSO plus chemotherapy extended median PFS by 9.5 months (based on HR of 0.62; 95% CI 0.48-0.80; p=0.0002). Importantly, a clinically meaningful PFS benefit was observed across all prespecified subgroups, including patients with central nervous system metastasis. In this group, the combination reduced the risk of disease progression or death by 53% compared to TAGRISSO monotherapy (based on a HR of 0.47; 95% CI 0.33-0.66), extending median PFS by 11.1 months versus TAGRISSO alone. At the time of this analysis, the overall survival (OS) data were immature, however, a favorable trend was observed for TAGRISSO plus chemotherapy. The trial continues to assess OS as a key secondary endpoint. The safety pro TAGRISSO plus chemotherapy was generally manageable and consistent with the established profiles of the individual medicines. Adverse event rates were higher in the combination arm, driven by well-characterized chemotherapy-related adverse events. Additional safety information will be presented at a forthcoming medical meeting. In August 2023, TAGRISSO in combination with chemotherapy received Breakthrough Therapy Designation by the FDA in this setting for the 1st-line treatment of adult patients with locally advanced or metastatic EGFRm NSCLC. TAGRISSO is approved as monotherapy in more than 100 countries including in the US, EU, China and Japan. Approved indications include for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant treatment of early-stage (IB, II and IIIA) EGFRm NSCLC. IMPORTANT SAFETY INFORMATION There are no contraindications for TAGRISSO Interstitial lung disease (ILD)/pneumonitis occurred in 3.7% of the 1479 TAGRISSO-treated patients; 0.3% of cases were fatal. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (eg, dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed Heart rate-corrected QT (QTc) interval prolongation occurs in TAGRISSO-treated patients. Of the 1479 TAGRISSO-treated patients in clinical trials, 0.8% were found to have a QTc >500 msec, and 3.1% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia Cardiomyopathy occurred in 3% of the 1479 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 3.2% of 1233 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. Conduct cardiac monitoring, including assessment of LVEF at baseline and during treatment, in patients with cardiac risk factors. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO Keratitis was reported in 0.7% of 1479 patients treated with TAGRISSO in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist Postmarketing cases consistent with Stevens-Johnson syndrome (SJS) and erythema multiforme major (EMM) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if SJS or EMM is suspected and permanently discontinue if confirmed Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology can be identified, consider permanent discontinuation of TAGRISSO based on severity Aplastic anemia has been reported in patients treated with TAGRISSO in clinical trials (0.07% of 1479) and post marketing. Some cases had a fatal outcome. Inform patients of the signs and symptoms of aplastic anemia including but not limited to, new or persistent fevers, bruising, bleeding, and pallor. If aplastic anemia is suspected, withhold TAGRISSO and obtain a hematology consultation. If aplastic anemia is confirmed, permanently discontinue TAGRISSO. Perform complete blood count with differential before starting TAGRISSO, periodically throughout treatment, and more frequently if indicated Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose Most common (≥20%) adverse reactions, including laboratory abnormalities, were leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough INDICATIONS TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with 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 first-line treatment of adult 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 adult 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 Prescription Information, including Patient Information for TAGRISSO. You may report side effects related to AstraZeneca products by clicking here. Notes Lung cancer Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.2 Lung cancer is broadly split into NSCLC and small cell lung cancer.3 The majority of all NSCLC patients are diagnosed with advanced disease.5 Patients with EGFRm NSCLC are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which blocks the cell-signaling pathways that drive the growth of tumor cells.9 FLAURA2 FLAURA2 is a randomized, open-label, multi-center, global Phase III trial in the 1st-line treatment of patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients were treated with TAGRISSO 80mg once daily oral tablets in combination with chemotherapy (pemetrexed (500mg/m2) plus cisplatin (75mg/m2) or carboplatin (AUC5) every three weeks for four cycles, followed by TAGRISSO with pemetrexed maintenance every three weeks. The trial enrolled 557 patients in more than 150 centers across more than 20 countries, including in the US, Europe, South America and Asia. The primary endpoint is PFS. The trial is ongoing and will continue to assess the secondary endpoint of OS. TAGRISSO® TAGRISSO® (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against CNS metastasis. TAGRISSO (40mg and 80mg once-daily oral tablets) has been used to treat nearly 700,000 patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFRm NSCLC. There is an extensive body of evidence supporting the use of TAGRISSO in EGFRm NSCLC. TAGRISSO is the only targeted therapy to improve survival in both early-stage disease in the ADAURA Phase III trial and late-stage disease in the FLAURA Phase III trial. AstraZeneca also has several ongoing Phase III trials focused on earlier stages of lung cancer, including a trial in the Stage IA2-IA3 adjuvant resectable setting (ADAURA2), in the neoadjuvant setting (NeoADAURA), and in the Stage III locally advanced unresectable setting (LAURA). The Company is also researching ways to address tumor mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III trial, which test TAGRISSO plus savolitinib, an oral, potent and highly selective MET TKI, as well as other potential new medicines. AstraZeneca in lung cancer AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most. The Company's comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including TAGRISSO and gefitinib; durvalumab and tremelimumab-actl; fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan in collaboration with Daiichi Sankyo; savolitinib in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action. AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment. 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 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit and follow us on social media @AstraZeneca. References 1. FDA. Priority Review. Available at: . Accessed September 2023. 2. World Health Organisation. International Agency for Research on Cancer. Lung Fact Sheet. Available at . Accessed September 2023. 3. LUNGevity Foundation. Types of Lung Cancer. Available at . Accessed September 2023. 4. Cheema PK, et al. Perspectives on treatment advances for stage III locally advanced unresectable non-small-cell lung cancer. Curr Oncol. 2019;26(1):37-42. 5. Cancer.Net. Lung Cancer - Non-Small Cell: Statistics. Available at: . Accessed September 2023. 6. Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol. 2013:6;2800-12. 7. Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011:29;2121-27. 8. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013:66;79-89. 9. Cross DA, et al. AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer. Cancer Discov. 2014;4(9):1046-1061.

Combination reduced the risk of disease progression by 38% versus TAGRISSO monotherapy, the current 1st-line global standard of care WILMINGTON, Del.--(BUSINESS WIRE)-- Positive results from the FLAURA2 Phase III trial showed AstraZeneca’s TAGRISSO® (osimertinib) in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), compared to TAGRISSO alone for patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). These results were presented today in a Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer (WCLC) (abstract #PL03). Results showed TAGRISSO plus chemotherapy reduced the risk of disease progression or death by 38% compared to TAGRISSO alone (based on a hazard ratio [HR] of 0.62; 95% confidence interval [CI] 0.49-0.79; p<0.0001). By investigator assessment, the combination extended median PFS by 8.8 months versus TAGRISSO alone. PFS results from blinded independent central review (BICR) were consistent, showing TAGRISSO plus chemotherapy extended median PFS by 9.5 months (based on HR of 0.62; 95% CI 0.48-0.80; p=0.0002). Importantly, a clinically meaningful PFS benefit was observed across all prespecified subgroups, including sex, race, type of EGFR mutation, age at time of diagnosis, smoking history and central nervous system (CNS) metastasis status at baseline. At the time of this analysis, the overall survival (OS) data were immature however, a favorable trend was observed for TAGRISSO plus chemotherapy. Pasi A. Jänne, MD, PhD, medical oncologist at Dana-Farber Cancer Institute and principal investigator for the FLAURA2 trial, said: “Patients received nearly nine additional months before their EGFR-mutated non-small cell lung cancer progressed as a result of the addition of chemotherapy to standard-of-care osimertinib, building on the strong efficacy we have already seen with osimertinib monotherapy. With these convincing data, patients may soon have a choice of two highly effective osimertinib-based treatment options in this advanced disease setting.” Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The compelling FLAURA2 results add to the extensive evidence supporting TAGRISSO as the backbone therapy in EGFR-mutated non-small cell lung cancer and establish a new benchmark for progression-free survival in this setting. We look forward to bringing this potential treatment regimen to patients with advanced lung cancer to further delay disease progression, especially for patients with the greatest unmet need including those with central nervous system metastasis at diagnosis.” Summary of results: FLAURA2 PFS by INV PFS by BICR TAGRISSO plus chemotherapy (n=279) TAGRISSO monotherapy (n=278) TAGRISSO plus chemotherapy (n=279) TAGRISSO monotherapy (n=278) Median PFS (in months)i 25.5 (24.7, NCii) 16.7 (14.1, 21.3) 29.4 (25.1, NCii) 19.9 (16.6, 25.3) Hazard ratio (95% CI) 0.62 (0.49-0.79) 0.62 (0.48-0.80) p-value <0.0001 0.0002 Data maturity 51% 43% i. Data cut-off date was 3 April 2023. ii. NC: Not calculable Safety results and discontinuation rates due to adverse events (AEs) were consistent with the established profiles of each medicine and no new safety concerns were reported. Grade 3 or higher AEs from all causes occurred in 64% of patients in the TAGRISSO plus chemotherapy arm versus 27% in the TAGRISSO monotherapy arm. IMPORTANT SAFETY INFORMATION There are no contraindications for TAGRISSO Interstitial lung disease (ILD)/pneumonitis occurred in 3.8% of the 1479 TAGRISSO-treated patients; 0.3% of cases were fatal. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (eg, dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed Heart rate-corrected QT (QTc) interval prolongation occurs in TAGRISSO-treated patients. Of the 1479 TAGRISSO-treated patients in clinical trials, 0.8% were found to have a QTc >500 msec, and 3.1% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia Cardiomyopathy occurred in 3% of the 1479 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 3.2% of 1233 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. Conduct cardiac monitoring, including assessment of LVEF at baseline and during treatment, in patients with cardiac risk factors. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO Keratitis was reported in 0.7% of 1479 patients treated with TAGRISSO in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist Postmarketing cases consistent with erythema multiforme major (EMM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if EMM, SJS, or TEN is suspected and permanently discontinue if confirmed. Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology can be identified, consider permanent discontinuation of TAGRISSO based on severity Aplastic anemia has been reported in patients treated with TAGRISSO in clinical trials (0.07% of 1479) and postmarketing. Some cases had a fatal outcome. Inform patients of the signs and symptoms of aplastic anemia including but not limited to, new or persistent fevers, bruising, bleeding, and pallor. If aplastic anemia is suspected, withhold TAGRISSO and obtain a hematology consultation. If aplastic anemia is confirmed, permanently discontinue TAGRISSO. Perform complete blood count with differential before starting TAGRISSO, periodically throughout treatment, and more frequently if indicated Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose Most common (≥20%) adverse reactions, including laboratory abnormalities, were leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough INDICATIONS TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with 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 first-line treatment of adult 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 adult 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 for TAGRISSO. You may report side effects related to AstraZeneca products by clicking here. Notes Lung cancer Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into NSCLC and small cell lung cancer.2 Each year, there are an estimated 2.2 million people diagnosed with lung cancer globally with 80-85% of patients diagnosed with NSCLC, the most common form of lung cancer.1-3 Approximately 70% of people are diagnosed with advanced NSCLC.4 Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.5-7 Patients with EGFRm NSCLC are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which blocks the cell-signalling pathways that drive the growth of tumour cells.8 FLAURA2 FLAURA2 is a randomized, open-label, multi-center, global Phase III trial in the 1st-line treatment of patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients were treated with TAGRISSO 80mg once daily oral tablets in combination with chemotherapy (pemetrexed (500mg/m2) plus cisplatin (75mg/m2) or carboplatin (AUC5)) every three weeks for four cycles, followed by TAGRISSO with pemetrexed maintenance every three weeks. The trial enrolled 557 patients in more than 150 centers across more than 20 countries, including in the US, Europe, South America and Asia. This is the analysis of the primary endpoint of PFS. The trial is ongoing and will continue to assess the secondary endpoint of OS. TAGRISSO® TAGRISSO® (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastasis. TAGRISSO (40mg and 80mg once-daily oral tablets) has been used to treat nearly 700,000 patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFRm NSCLC. TAGRISSO, the only targeted therapy to improve survival in both early- and late-stages of EGFRm NSCLC, is approved as monotherapy in more than 100 countries including in the US, EU, China and Japan. These include for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC (FLAURA), locally advanced or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant treatment of early-stage (IB, II and IIIA) EGFRm NSCLC (ADAURA), where TAGRISSO recently demonstrated a statistically significant and clinically meaningful OS benefit. AstraZeneca also has several ongoing Phase III trials focused on earlier stages of lung cancer including a trial in the Stage IA2-IA3 adjuvant resectable setting (ADAURA2), and in the Stage III locally advanced unresectable setting (LAURA). The Company is also researching ways to address tumor mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III trial, which test TAGRISSO plus savolitinib, an oral, potent and highly selective MET TKI, as well as other potential new medicines. AstraZeneca in lung cancer AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most. The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including tremelimumab-actl and gefitinib; durvalumab and tremelimumab-actl; fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan in collaboration with Daiichi Sankyo; savolitinib in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action. AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment. 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 (LSE/STO/Nasdaq: AZN) 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 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca-us.com and follow the Company on Social Media @AstraZeneca. References World Health Organisation. International Agency for Research on Cancer. Lung Fact Sheet. Available at . Accessed August 2023. LUNGevity Foundation. Types of Lung Cancer. Available at . Accessed August 2023. Cheema PK, et al. Perspectives on treatment advances for stage III locally advanced unresectable non-small-cell lung cancer. Curr Oncol. 2019;26(1):37-42. Cancer.Net. Lung Cancer - Non-Small Cell: Statistics. Available at: . Accessed August 2023. Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol. 2013:6;2800-12. Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011:29;2121-27. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013:66;79-89. Cross DA, et al. AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer. Cancer Discov. 2014;4(9):1046-1061. US-80077 Last Updated 09/23

WILMINGTON, Del.--( BUSINESS WIRE )--Positive results from the ADAURA Phase III trial showed AstraZeneca’s TAGRISSO ® (osimertinib) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), compared to placebo in the adjuvant treatment of patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after complete tumor resection with curative intent. These results will be presented today in an oral presentation during the Plenary Session at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (abstract #LBA3). TAGRISSO reduced the risk of death by 51% compared to placebo in both the primary analysis population (Stages II-IIIA) (21% data maturity, OS hazard ratio [HR] of 0.49; 95.03% confidence interval [CI] 0.33-0.73; p=0.0004), and in the overall trial population (Stages IB-IIIA) (18% data maturity, OS HR of 0.49; 95.03% CI 0.34-0.70; p<0.0001). In the primary analysis population, an estimated 85% of patients treated with TAGRISSO were alive at five years compared to 73% on placebo. In the overall trial population, an estimated 88% of patients treated with TAGRISSO were alive at five years compared to 78% on placebo. Median OS was not yet reached in either population or treatment group. Patients on placebo that recurred with metastatic disease had the opportunity to receive TAGRISSO as a subsequent treatment. Roy S. Herbst, MD, PhD, Deputy Director and Chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital, New Haven, Connecticut, US, and principal investigator in the trial, said: “ These highly anticipated overall survival results, with 88 per cent of patients alive at five years, are a momentous achievement in the treatment of early-stage EGFR-mutated lung cancer. These data underscore that adjuvant treatment with osimertinib provides patients with the best chance of long-term survival.” Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “ TAGRISSO cut the risk of death by more than half in the adjuvant setting, further establishing this transformative medicine as the backbone treatment for EGFR-mutated lung cancer. These results emphasize the importance of diagnosing patients with lung cancer early, testing for EGFR mutations and treating all those with an EGFR mutation with TAGRISSO.” Summary of OS results: ADAURA i TAGRISSO Placebo Stages II-IIIA (primary population) (n=233) (n=237) Median OS (in months) Not reached Not reached Hazard ratio (95.03% CI) 0.49 (0.33-0.73) p-value 0.0004 OS rate (%) (five years) (95% CI) 85 (79-89) 73 (66-78) Stage IB-IIIA (overall population) (n=339) (n=343) Median OS (in months) Not reached Not reached Hazard ratio (95.03% CI) 0.49 (0.34-0.70) p-value <0.0001 OS rate (%) (five years) (95% CI) 88 (83-91) 78 (73-82) i The data cut-off date was 27 January, 2023. At the previously reported disease-free survival analysis, all patients had completed or discontinued treatment. The safety and tolerability of TAGRISSO with extended follow-up were consistent with its established profile and previous analyses with no new safety concerns reported. Adverse events at Grade 3 or higher from all causes occurred in 23% of patients in the TAGRISSO arm versus 14% in the placebo arm. IMPORTANT SAFETY INFORMATION There are no contraindications for TAGRISSO Interstitial lung disease (ILD)/pneumonitis occurred in 3.7% of the 1479 TAGRISSO-treated patients; 0.3% of cases were fatal. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (eg, dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed Heart rate-corrected QT (QTc) interval prolongation occurs in TAGRISSO-treated patients. Of the 1479 TAGRISSO-treated patients in clinical trials, 0.8% were found to have a QTc >500 msec, and 3.1% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia Cardiomyopathy occurred in 3% of the 1479 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 3.2% of 1233 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. Conduct cardiac monitoring, including assessment of LVEF at baseline and during treatment, in patients with cardiac risk factors. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO Keratitis was reported in 0.7% of 1479 patients treated with TAGRISSO in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist Postmarketing cases consistent with Stevens-Johnson syndrome (SJS) and erythema multiforme major (EMM) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if SJS or EMM is suspected and permanently discontinue if confirmed Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology can be identified, consider permanent discontinuation of TAGRISSO based on severity Aplastic anemia has been reported in patients treated with TAGRISSO in clinical trials (0.07% of 1479) and postmarketing. Some cases had a fatal outcome. Inform patients of the signs and symptoms of aplastic anemia including but not limited to, new or persistent fevers, bruising, bleeding, and pallor. If aplastic anemia is suspected, withhold TAGRISSO and obtain a hematology consultation. If aplastic anemia is confirmed, permanently discontinue TAGRISSO. Perform complete blood count with differential before starting TAGRISSO, periodically throughout treatment, and more frequently if indicated Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose Most common (≥20%) adverse reactions, including laboratory abnormalities, were leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough INDICATIONS TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with 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 first-line treatment of adult 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 adult 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 for TAGRISSO. You may report side effects related to AstraZeneca products by clicking here . Notes Lung cancer Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths. 1 Lung cancer is broadly split into NSCLC and small cell lung cancer. 2 The majority of all NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis. 4‑5 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition. 7‑8 For patients with resectable tumors, the majority eventually develop recurrence despite complete tumor resection and adjuvant chemotherapy. 9 ADAURA ADAURA was a randomized, double-blind, placebo-controlled, global Phase III trial in the adjuvant treatment of 682 patients with Stage IB, II, IIIA EGFRm NSCLC following complete tumor resection and, at physicians’ and patients’ discretion, adjuvant chemotherapy. Patients were treated with TAGRISSO 80mg once-daily oral tablets or placebo for three years or until disease recurrence. The trial was enrolled in more than 200 centers across more than 20 countries, including the US, Europe, South America, Asia and the Middle East. The primary endpoint was DFS in Stage II and IIIA patients and key secondary endpoints included DFS in Stage IB, II and IIIA patients, and OS in both the primary and overall populations. Though the primary data readout was originally anticipated in 2022, data from the trial were reported early following a recommendation from an Independent Data Monitoring Committee (IDMC) based on its determination of overwhelming efficacy. TAGRISSO ® TAGRISSO ® (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases. TAGRISSO (40mg and 80mg once-daily oral tablets) has been used to treat nearly 700,000 patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFRm NSCLC. In addition to investigating TAGRISSO in early-stage disease, AstraZeneca is also studying the medicine in combination with chemotherapy in locally advanced and metastatic EGFRm NSCLC (FLAURA2). The Company is also researching ways to address tumor mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III trial, which test TAGRISSO given concomitantly with savolitinib, an oral, potent and highly selective MET TKI, as well as other potential new medicines. AstraZeneca in lung cancer AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most. The Company's comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including tremelimumab-actl and gefitinib; durvalumab and tremelimumab-actl; fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan in collaboration with Daiichi Sankyo; savolitinib in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action. AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment. 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 100 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 Twitter @AstraZenecaUS . References World Health Organisation. International Agency for Research on Cancer. Lung Fact Sheet. Available at https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf . Accessed March 2023. LUNGevity Foundation. Types of Lung Cancer. Available at https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer . Accessed March 2023. Cheema PK, et al. Perspectives on treatment advances for stage III locally advanced unresectable non-small-cell lung cancer. Curr Oncol. 2019;26(1):37-42. Cagle P, et al. Lung Cancer Biomarkers: Present Status and Future Developments. Archives Pathology Lab Med. 2013;137:1191-1198. Le Chevalier T, et al. Adjuvant Chemotherapy for Resectable Non-Small-Cell Lung Cancer: Where is it Going? Ann Oncol. 2010;21:vii196-vii198. Goldstraw P, et al. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol. 2016;11(1):39-51. Sethi S, et al. Incidental Nodule Management – Should There Be a Formal Process? J Thorac Oncol. 2016:8;S494-S497. LUNGevity Foundation. Screening and Early Detection. Available at https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection . Accessed March 2023. Pignon et al. Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26:3552-3559.