AstraZeneca’s Tagrisso Receives EU Recommendation as First Targeted Therapy for Unresectable EGFR-Mutated Lung Cancer

(IN BRIEF) AstraZeneca’s Tagrisso (osimertinib) has been recommended for approval in the EU for treating adult patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) with EGFR mutations who have not experienced disease progression after platinum-based chemoradiation therapy. This recommendation follows the LAURA Phase III trial, which showed Tagrisso significantly extended progression-free survival to 39.1 months compared to 5.6 months with placebo, reducing the risk of progression or death by 84%. Tagrisso is already approved for similar indications in the US, and regulatory reviews are ongoing globally. If approved, it would be the first targeted therapy for this patient group in Europe.

(PRESS RELEASE) CAMBRIDGE, 19-Nov-2024 — /EuropaWire/ — The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive recommendation for AstraZeneca’s Tagrisso (osimertinib), paving the way for its approval in the European Union. If approved, Tagrisso will be the first targeted therapy available for adult patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. This treatment applies to patients whose disease has not progressed during or after platinum-based chemoradiation therapy (CRT).

Groundbreaking Results from the LAURA Phase III Trial

The CHMP’s recommendation is based on findings from the LAURA Phase III trial, recently published in The New England Journal of Medicine. The study demonstrated that Tagrisso significantly reduced the risk of disease progression or death by 84% compared to placebo (hazard ratio [HR] 0.16; 95% CI 0.10-0.24; p<0.001). Patients treated with Tagrisso achieved a median progression-free survival (PFS) of 39.1 months, compared to just 5.6 months for those on placebo.

While overall survival (OS) data remain immature, further analysis is ongoing as OS is a secondary endpoint of the trial.

A Critical Advancement in Lung Cancer Treatment

In Europe, lung cancer impacts more than 450,000 individuals annually, with NSCLC being the most common type. Around 10-15% of NSCLC patients have EGFR mutations, and nearly 20% present with unresectable tumors. Despite advances in oncology, this population faces significant unmet medical needs.

Dr. Manuel Cobo, Medical Oncology Specialist at Carlos Haya University Hospital in Malaga, Spain, and an investigator in the LAURA trial, highlighted the importance of this milestone:
“LAURA’s results demonstrate the efficacy of osimertinib and underscore its potential as the first targeted therapy for unresectable, EGFR-mutated lung cancer. Patients in Europe could soon have access to a treatment that extends the time before disease progression by more than three years.”

Susan Galbraith, AstraZeneca’s Executive Vice President of Oncology R&D, added:
“Tagrisso has solidified its role as the backbone therapy for EGFR-mutated NSCLC across all stages of the disease. This recommendation marks a significant step forward in addressing the urgent need for innovative therapies that can improve outcomes for patients with unresectable tumors.”

Expanding Global Approvals

Tagrisso has already gained approval in the United States for treating unresectable Stage III EGFR-mutated NSCLC following CRT. Regulatory reviews are underway in several countries, including China and Japan. Globally, Tagrisso is approved in over 100 countries for various EGFR-mutated NSCLC indications, including early-stage adjuvant therapy, first-line metastatic treatment, and combination therapy with chemotherapy in select cases.

Safety and Tolerability

The safety profile of Tagrisso observed in the LAURA trial was consistent with previous studies, with no new safety concerns reported.

With this positive CHMP recommendation, Tagrisso is poised to transform care for patients with EGFR-mutated, unresectable NSCLC, offering a targeted solution to significantly delay disease progression.

Notes

Lung cancer
Each year, an estimated 2.4 million people are diagnosed with lung cancer globally.5 Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.5 Lung cancer is broadly split into NSCLC and small cell lung cancer.3 The majority of all NSCLC patients are diagnosed with advanced disease.6

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.7-9 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.10

LAURA
LAURA is a randomised, double-blind, placebo-controlled, multi-centre, global Phase III trial in patients with unresectable, Stage III EGFRm NSCLC whose disease has not progressed following definitive platinum-based CRT. Patients were treated with Tagrisso 80mg once-daily oral tablets until disease progression, unacceptable toxicity or other discontinuation criteria were met. Upon progression, patients in the placebo arm were offered treatment with Tagrisso.

The trial enrolled 216 patients in more than 145 centres across more than 15 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 central nervous system (CNS) metastases. Tagrisso (40mg and 80mg once-daily oral tablets) has been used to treat 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 as standard of care in EGFRm NSCLC. Tagrisso improved patient outcomes in early-stage disease in the ADAURA Phase III trial, Stage III, unresectable disease in the LAURA Phase III trial, late-stage disease in the FLAURA Phase III trial, and with chemotherapy in the FLAURA2 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 neoadjuvant setting in the NeoADAURA Phase III trial and in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial.

The Company is also researching ways to address tumour mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III trial, which test Tagrisso plus savolitinib 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 Iressa (gefitinib); Imfinzi (durvalumab) and Imjudo (tremelimumab); Enhertu (trastuzumab deruxtecan) and 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.

References

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Sanden SV, et al. Prevalence of Epidermal Growth Factor Receptor Exon 20 Insertion Mutations in Non-small-Cell Lung Cancer in Europe: A Pragmatic Literature Review and Meta-analysis. Targeted Onc. 2022;17:153-166.
LUNGevity Foundation. Types of Lung Cancer. Available at: https://www.lungevity.org/lung-cancer-basics/types-of-lung-cancer. Accessed November 2024.
Quint LE. Lung cancer: assessing resectability. Cancer Imaging. 2004;4(1):15-18.
World Health Organization. International Agency for Research on Cancer. All Cancers Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/39-all-cancers-fact-sheet.pdf. Accessed November 2024.
Cagle P, et al. Lung Cancer Biomarkers: Present Status and Future Developments. Arch Pathol Lab Med. 2013;137(9):1191-1198.
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(15):2121-2127.
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(12): 2800-2812.
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(2):79-89.
Cross DAE, et al. AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer. Cancer Discov. 2014;4(9):1046-1061.

Adrian Kemp
Company Secretary
AstraZeneca PLC

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SOURCE: AstraZeneca

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