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-characterised 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%).

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 randomised, open-label, multi-centre, 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 80mg QD oral tablets with the addition of 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 centres 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 (40mg and 80mg 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 Orpathys (savolitinib) in the SAFFRON Phase III trial and in combination with Datroway (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 Iressa (gefitinib); Imfinzi (durvalumab) and Imjudo (tremelimumab); Enhertu (trastuzumab deruxtecan) and Datroway (datopotamab deruxtecan) in collaboration with Daiichi Sankyo; Orpathys (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 catalyse 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 (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation 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 astrazeneca.com and follow the Company on social media @AstraZeneca.

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References

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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.
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