Company Announcements

FLAURA2 final overall survival analysis reinforces the favorable benefit-risk profile of this combination

Results underscore TAGRISSO as 1st-line standard of care and backbone therapy in EGFRm lung cancer across stages

WILMINGTON, Del.--(BUSINESS WIRE)--Sep. 7, 2025-- Positive results from the final overall survival (OS) analysis of the FLAURA2 Phase III trial showed AstraZeneca’s TAGRISSO^®(osimertinib) with the addition of pemetrexed and platinum-based chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the key secondary endpoint of OS compared to TAGRISSO monotherapy in the 1st-line treatment of patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC).

These results will be presented today during the Presidential Symposium at the IASLC 2025 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer in Barcelona, Spain (abstract #PL02.04).

In the final OS analysis, TAGRISSO plus chemotherapy demonstrated a median OS of nearly four years (47.5 months) compared to approximately three years (37.6 months) for TAGRISSO monotherapy. At 57% data maturity, results showed TAGRISSO plus chemotherapy reduced the risk of death by 23% compared to TAGRISSO monotherapy (based on a hazard ratio [HR] of 0.77; 95% confidence interval [CI] 0.61-0.96; p=0.0202). An estimated 63.1% of patients treated with the combination were alive at three years and 49.1% of patients were alive at four years compared to 50.9% and 40.8%, respectively, in the monotherapy arm. Importantly, the observed OS benefit for TAGRISSO plus chemotherapy versus TAGRISSO monotherapy was consistent across all prespecified subgroups. Patients in the control arm received standard of care, including chemotherapy, upon progression, supporting the relevance of the OS results.

David Planchard, MD, PhD, Thoracic Oncologist at Gustave Roussy Institute of Oncology, Villejuif, France, and principal investigator for the trial, said: “The fundamental goals of lung cancer treatment are to extend survival while preserving patients' quality of life. These compelling results, which demonstrated unprecedented median overall survival, show this combination can achieve both of these goals and support osimertinib, with or without the addition of chemotherapy, as the standard of care for patients with 1st-line advanced EGFR-mutated lung cancer. With two highly effective osimertinib-based options for these patients, physicians can better tailor treatment to individual needs and help ensure the best possible outcome for each patient.”

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “The latest FLAURA2 trial results set a new survival standard for patients, with TAGRISSO plus chemotherapy demonstrating a median overall survival of nearly four years in 1st-line advanced EGFR-mutated lung cancer—surpassing the three-year benchmark established in the FLAURA trial. Over the past decade, TAGRISSO has consistently delivered strong survival benefits and tolerable safety across all stages of non-small cell lung cancer, cementing its role as the backbone therapy in EGFR-mutated lung cancer.”

Summary of OS results: FLAURA2

1. OS data cut-off date was 12 June 2025
2. Median follow-up duration for OS in censored patients at data cut-off: 51.2 (0.2-60.4) months for TAGRISSO plus chemotherapy and 51.3 (0.1-60.1) months for TAGRISSO monotherapy
3. Calculated by Kaplan–Meier method
4. Not calculable
5. For statistical significance, a 2-sided p-value of less than 0.04953, as determined by the O’Brien and Fleming spending rule, was required

With longer follow-up, the safety profile of TAGRISSO plus chemotherapy continued to be manageable and consistent with the established profiles of the individual medicines. Grade 3 or higher adverse events (AEs) from all causes occurred in 70% of patients in the TAGRISSO plus chemotherapy arm, driven by well-characterized chemotherapy-related AEs, versus 34% in the TAGRISSO monotherapy arm, similar to the rates reported at the primary analysis presented at the IASLC 2023 WCLC (64% versus 27%, respectively). Discontinuation rates due to AEs and on-target toxicities were low in both trial arms (12% versus 7%).

IMPORTANT SAFETY INFORMATION

• There are no contraindications for TAGRISSO

• TAGRISSO can cause severe and fatal interstitial lung disease (ILD)/pneumonitis. ILD/pneumonitis occurred in 4% of the 1813 patients treated with TAGRISSO monotherapy who had not received recent definitive chemoradiation therapy (CRT); 0.4% of cases were fatal. In the FLAURA2 study, ILD/pneumonitis occurred in 3.3% of the 276 patients who received TAGRISSO in combination with pemetrexed and platinum-based chemotherapy; 0.4% of cases were fatal. For patients receiving TAGRISSO who have not received recent definitive platinum-based CRT, withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Permanently discontinue TAGRISSO if ILD/pneumonitis is confirmed

• TAGRISSO can cause heart rate-corrected QT (QTc) interval prolongation. Of the 1813 TAGRISSO monotherapy-treated patients in clinical trials, 1.1% were found to have a QTc >500 msec, and 4.3% of patients had an increase from baseline QTc >60 msec. Of the 276 patients treated with TAGRISSO in combination with pemetrexed and platinum-based chemotherapy in the FLAURA2 study, 1.8% were found to have a QTc >500 msec, and 10.5% 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

• TAGRISSO can cause cardiomyopathy, including cardiac failure, chronic cardiac failure, congestive heart failure, pulmonary edema or decreased ejection fraction. Cardiomyopathy occurred in 3.8% of the 1813 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. In the FLAURA2 study, cardiomyopathy occurred in 9% of the 276 patients who received TAGRISSO in combination with pemetrexed and platinum-based chemotherapy; 1.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 4.2% of 1557 patients who had baseline and at least one follow-up LVEF assessment. In the FLAURA2 study, 8% (21/262) of patients treated with TAGRISSO in combination with pemetrexed and platinum-based chemotherapy, who had baseline and at least one follow-up LVEF assessment, experienced LVEF decreases ≥10% and a drop to <50%. For patients receiving TAGRISSO monotherapy, conduct cardiac monitoring in patients with cardiac risk factors, including assessment of LVEF at baseline and during treatment. For patients receiving TAGRISSO in combination with pemetrexed and platinum-based chemotherapy, conduct cardiac monitoring in all patients, including assessment of LVEF at baseline and during treatment. 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 0.6% of 1813 patients treated with TAGRISSO monotherapy 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 (0.06% of 1813) 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 last dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the last dose

• Because of the potential for serious adverse reactions in breastfed infants from TAGRISSO, women should not breastfeed during treatment with TAGRISSO and for 2 weeks after the last dose

• Most common (≥20%) adverse reactions, including laboratory abnormalities, were:
  
  
  • TAGRISSO in combination with pemetrexed and platinum-based chemotherapy: leukopenia, thrombocytopenia, neutropenia, lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry skin, and increased blood creatinine

INDICATIONS

• TAGRISSO is indicated in combination with pemetrexed and platinum-based chemotherapy, for the first-line treatment of adult patients with locally advanced or metastatic NSCLC whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test

Please see complete Prescribing Information , including Patient Information for TAGRISSO.

Notes
NSCLC
Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.¹ Lung cancer is broadly split into small cell lung cancer or NSCLC, the latter accounting for 80-85% of cases.^1-2 Approximately 75% of people are diagnosed with advanced NSCLC.³ Additionally, about 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.^4-6

While EGFR-tyrosine kinase inhibitors (TKI) have significantly improved outcomes in the 1st-line setting, mechanisms of resistance and disease progression are extremely common, and a significant unmet need exists in later-line settings for effective and well-tolerated treatment options.^7-10

FLAURA2
FLAURA2 is a randomized, open-label, multi-center, global Phase III trial in previously untreated patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) NSCLC whose tumors have EGFR exon 19 deletion or exon 21 L858R mutations. Patients were treated with TAGRISSO 80 mg QD oral tablets with the addition of chemotherapy (pemetrexed (500 mg/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 with OS as the key secondary endpoint.

TAGRISSO
TAGRISSO^® (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases. TAGRISSO (40 mg and 80 mg QD oral tablets) has been used to treat more than one million patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFRm NSCLC.

TAGRISSO is approved as monotherapy in more than 120 countries including 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, adjuvant treatment of early-stage EGFRm NSCLC and locally advanced, unresectable NSCLC following platinum-based chemoradiation therapy (CRT). TAGRISSO is also approved in combination with chemotherapy in more than 80 countries, including the US, EU, China and Japan, for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC.

There is an extensive body of evidence supporting the use of TAGRISSO in EGFRm NSCLC, and it is the only targeted therapy shown to improve patient outcomes across all stages of the disease.

In late-stage disease, TAGRISSO demonstrated improved outcomes as monotherapy in the FLAURA Phase III trial and in combination with chemotherapy in the FLAURA2 Phase III trial. TAGRISSO is also being investigated in this setting in combination with savolitinib in the SAFFRON Phase III trial and in combination with datopotamab deruxtecan or Dato-DXd in the TROPION-Lung14 and TROPION-Lung15 Phase III trials.

TAGRISSO also showed improved outcomes in early-stage disease in the NeoADAURA and ADAURA Phase III trials and in locally advanced stages in the LAURA Phase III trial. As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, TAGRISSO is also being investigated in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial.

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 in 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.

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’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow the Company on social media @AstraZeneca.

References

1. World Health Organization. International Agency for Research on Cancer. Lung Cancer Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf. Accessed August 2025.
2. American Cancer Society. What Is Lung Cancer?. Available at: https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html. Accessed August 2025.
3. Chen HJ, et al. Long-term survival of advanced lung adenocarcinoma by maintenance chemotherapy followed by EGFR-TKI. Medicine. 2021;100(6):e24688.
4. 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.
5. 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;6:2800-2812.
6. 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.
7. Chen R, et al. Emerging therapeutic agents for advanced non-small cell lung cancer. J Hematol Oncol. 2020;13(1):58.
8. Majeed U, et al. Targeted therapy in advanced non-small cell lung cancer: current advances and future trends. J Hematol Oncol. 2021;14(1):108.
9. Morgillo F, et al. Mechanisms of resistance to EGFR-targeted drugs: lung cancer. ESMO Open. 2016;1(3):e000060.
10. Han B, et al. Efficacy of pemetrexed-based regimens in advanced non-small cell lung cancer patients with activating epidermal growth factor receptor mutations after tyrosine kinase inhibitor failure: a systematic review. Onco Targets Ther. 2018;11:2121-2129.

US-101723 Last Updated 09/25

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