Positive results from the LAURA Phase III trial showed AstraZeneca's Tagrisso (osimertinib) demonstrated a statistically significant and highly clinically meaningful improvement in progression-free survival (PFS) for patients with unresectable, Stage III epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) whose tumours have exon 19 deletions or exon 21 (L858R) mutations, after chemoradiotherapy (CRT) compared to placebo after CRT.

These results will be presented today during the Plenary Session at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (abstract #LBA4) and simultaneously published in The New England Journal of Medicine. (https://www.nejm.org/doi/full/10.1056/NEJMoa2402614)

Results showed Tagrisso reduced the risk of disease progression or death by 84% compared to placebo (hazard ratio [HR] 0.16; 95% confidence interval [CI] 0.10-0.24; p<0.001) as assessed by blinded independent central review (BICR). Median PFS was 39.1 months in patients treated with Tagrisso versus 5.6 months for placebo. Importantly, a clinically meaningful PFS benefit was observed across all prespecified subgroups including sex, race, type of EGFR mutation, age, smoking history, and prior CRT.

Overall survival (OS) data showed a favourable trend for Tagrisso, although data were not mature at the time of this analysis. The trial will continue to assess OS as a secondary endpoint.

Suresh Ramalingam, MD, Executive Director of Winship Cancer Institute of Emory University, Atlanta, US and principal investigator in the trial, said: "The impressive progression-free survival results from the LAURA Phase III trial represent a major breakthrough for patients with Stage III EGFR-mutated lung cancer for whom no targeted treatments are available. Osimertinib delayed the risk of disease progression or death by an unprecedented 84% and should become the new standard of care for patients in this setting based on these data."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "Tagrisso extended progression-free survival by more than three years in this potentially curative setting, reinforcing the need to test and diagnose patients early. These practice-changing data cement the powerful impact Tagrisso can make as backbone therapy in EGFR-mutated lung cancer, especially in the lives of these patients who have historically experienced early progression following chemoradiotherapy."  

Summary of results: LAURA

[][][]
Tagrisso(n=143) Placebo(n=73)
Median PFS 39.1 (31.5, NC)[ii] 5.6 (3.7, 7.4)
(in
months)[i]
Hazard ratio 0.16 (0.10, 0.24)
(95% CI) 
p-value  <0.001[iii]
Data 56%
maturity  
40% 86%
i. Data cut
-off date
was January
5, 2024.ii.
NC: Not
calculable 
iii. Nominal
p-value

Safety results and discontinuation rates due to adverse events (AEs) were as expected and no new safety concerns were identified. Grade 3 or higher AEs from all causes occurred in 35% of patients in the Tagrisso arm versus 12% in the placebo arm.

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 EGFRm NSCLC. Tagrisso with the addition of chemotherapy is also approved in the US and several other countries for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC.

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] Each year there are an estimated 2.4 million people diagnosed with lung cancer globally, with 80-85% of patients diagnosed with NSCLC, the most common form of lung cancer. The majority of all NSCLC patients are diagnosed with advanced disease.[2-5]

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.[6-8] 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.[9]

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 permitted to be treated 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. 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) metastases. Tagrisso (40mg and 80mg once-daily oral tablets) has been used to treat nearly 800,000 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 patient outcomes in early-stage disease in the ADAURA Phase III trial (https://www.astrazeneca.com/media-centre/press-releases/2023/tagrisso-demonstrated-strong-overall-survival-benefit-in-the-adaura-phase-iii-trial.html), locally advanced stages in the LAURA Phase III trial (https://www.astrazeneca.com/media-centre/press-releases/2024/tagrisso-improved-pfs-in-stage-iii-lung-cancer.html) and late-stage disease in the FLAURA Phase III trial (https://www.astrazeneca.com/media-centre/press-releases/2019/tagrisso-significantly-improves-overall-survival-in-the-phase-iii-flaura-trial-for-1st-line-egfr-mutated-non-small-cell-lung-cancer-09082019.html) and FLAURA2 Phase III trial (https://www.astrazeneca.com/media-centre/press-releases/2023/tagrisso-plus-chemotherapy-extended-median-progression-free-survival-by-nearly-9-months-in-egfr-mutated-advanced-lung-cancer-in-flaura2-phase-iii-trial.html). 

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 with results expected later this year 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, 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 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 operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com (http://www.astrazeneca.com/) and follow the Company on social media @AstraZeneca (https://www.linkedin.com/company/astrazeneca).

Contacts

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References

1. FDA. Frequently Asked Questions: Breakthrough Therapies. Available at: https://www.fda.gov/regulatory-information/food-and-drug-administration-safety-and-innovation-act-fdasia/frequently-asked-questions-breakthrough-therapies. Accessed May 2024. 
2. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf. Accessed May 2024.  
3. LUNGevity Foundation. Types of Lung Cancer. Available at: https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer. Accessed May 2024. 
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. Cagle P, et al. Lung Cancer Biomarkers: Present Status and Future Developments. Archives Pathology Lab Med. 2013;137:1191-1198.
6. 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.
7. 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. 
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