• Treatment with adjuvant TAGRISSO reduced the risk of death by more than half

WILMINGTON, Del. / Jun 04, 2023 / 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: ADAURAⁱ

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.

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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

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