TAGRISSO® (osimertinib) reduced the risk of disease progression or death by 84% in patients with unresectable, Stage III EGFR-mutated lung cancer vs. placebo in LAURA Phase III trial

Rhea-AI Summary

AstraZeneca's TAGRISSO® (osimertinib) demonstrated a significant improvement in progression-free survival (PFS) for patients with unresectable, Stage III EGFR-mutated lung cancer, as shown in the LAURA Phase III trial. In the trial, TAGRISSO reduced the risk of disease progression or death by 84% compared to placebo (HR 0.16; 95% CI 0.10-0.24; p<0.001). Median PFS was 39.1 months for TAGRISSO versus 5.6 months for placebo. The trial included 216 patients and results were presented at the 2024 ASCO Annual Meeting and published in The New England Journal of Medicine. The study noted a favorable trend in overall survival, though data is still maturing. Safety results were consistent with previous studies, with Grade 3 or higher adverse events in 35% of TAGRISSO patients. TAGRISSO is already approved in over 100 countries for various indications. The drug's efficacy cements its role as a critical therapy in managing EGFR-mutated NSCLC.

Positive

• TAGRISSO reduced the risk of disease progression or death by 84% compared to placebo.
• Median progression-free survival (PFS) was 39.1 months with TAGRISSO versus 5.6 months with placebo.
• Favorable overall survival (OS) trend observed, though not yet mature.
• Safety results were consistent with previous studies; no new safety concerns identified.
• TAGRISSO is approved in over 100 countries for multiple indications.
• TAGRISSO is the first EGFR inhibitor to show benefit in the Stage III setting.

Negative

• Grade 3 or higher adverse events occurred in 35% of patients in the TAGRISSO arm, higher than 12% in the placebo arm.
• The overall survival (OS) data is not yet mature, creating uncertainty about long-term benefits.
• Potential risks include interstitial lung disease, QTc interval prolongation, cardiomyopathy, and other severe adverse effects.

Oncology Expert

TAGRISSO's results from the LAURA Phase III trial mark a significant breakthrough in the treatment of Stage III EGFR-mutated NSCLC. The prolongation of progression-free survival (PFS) to 39.1 months compared to 5.6 months with placebo is unprecedented. This substantial increase in PFS indicates that osimertinib can effectively delay disease progression, offering patients a longer period without symptoms or the need for further aggressive treatments.

The reduction in the risk of disease progression or death by 84% is noteworthy and could potentially shift the current treatment paradigm. Given the lack of targeted treatments for this patient group, TAGRISSO has the potential to become the new standard of care.

It's important for retail investors to understand that these results, especially when presented at a major conference like ASCO and published in the New England Journal of Medicine, can significantly bolster AstraZeneca's position in the oncology market.

Financial Analyst

The impressive clinical results for TAGRISSO are likely to have a positive financial impact on AstraZeneca. Extending PFS by more than three years in a setting where treatment options are limited can drive increased adoption among oncologists. This, in turn, will likely lead to higher sales volumes and revenue growth for AstraZeneca.

Investors should note that while the overall survival (OS) data are not yet mature, the favorable trend observed is promising. The continuation of the trial to assess OS as a secondary endpoint could further enhance TAGRISSO’s market potential.

Given TAGRISSO's existing global approvals and its potential to become the new standard of care for unresectable Stage III EGFR-mutated NSCLC, AstraZeneca is well-positioned to capture a significant share of this market segment.

Medical Research Analyst

The LAURA Phase III trial results add substantial evidence to the efficacy of TAGRISSO in treating early and locally advanced stages of EGFR-mutated NSCLC. The fact that TAGRISSO showed consistent benefit across all prespecified subgroups strengthens the generalizability of these findings. For investors, this means that the drug's market is not limited to a narrow demographic but has widespread applicability.

Understanding the nuances of the trial data, such as the hazard ratio (HR) of 0.16 and its 95% confidence interval (CI) of 0.10-0.24, is essential. These figures indicate a high level of statistical significance, which supports the robustness of the trial outcomes.

Safety remains a pivotal consideration. Although some Grade 3 or higher adverse events were noted, their incidence was manageable and not unexpected. For retail investors, this balance of efficacy and safety is a key factor in assessing the long-term viability of TAGRISSO in the market.

​​​First and only EGFR inhibitor and targeted treatment to show benefit in Stage III setting, extending progression-free survival by more than three years

WILMINGTON, Del.--(BUSINESS WIRE)-- 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 tumors 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.

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 favorable 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 (in months)i	​39.1 (31.5, NC)ii	​5.6 (3.7, 7.4)
​Hazard ratio (95% CI)	​ 0.16 (0.10, 0.24)
​p-value	<0.001iii
​Data maturity	​56%
	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.

IMPORTANT SAFETY INFORMATION

• There are no contraindications for TAGRISSO
• Interstitial lung disease (ILD)/pneumonitis occurred in 4% of the 1813 TAGRISSO-treated patients; 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. 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/pneumonitis is confirmed
• Heart rate-corrected QT (QTc) interval prolongation occurs in TAGRISSO-treated patients. 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
• 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 ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. 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 less than 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 final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final 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 final dose
• Most common (≥20%) adverse reactions, including laboratory abnormalities, were:
  • TAGRISSO monotherapy: leukopenia, lymphopenia, thrombocytopenia, anemia, diarrhea, rash, musculoskeletal pain, neutropenia, nail toxicity, dry skin, stomatitis, and fatigue
  • 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 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 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
• TAGRISSO is indicated for the treatment of adult patients with metastatic epidermal growth factor receptor (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 Prescription 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 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.^1-4

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.^5-7 Patients with EGFRm NSCLC are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which blocks the cell-signaling pathways that drive the growth of tumor cells.⁸

LAURA

LAURA is a randomized, double-blind, placebo-controlled, multi-center, 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 centers 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 (40 mg and 80 mg 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, locally advanced stages in the LAURA Phase III trial and late-stage disease in the FLAURA Phase III trial and 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 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 tumor 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 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. Please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca.

References

1. 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. ​
2. LUNGevity Foundation. Types of Lung Cancer. Available at: https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer. Accessed May 2024. ​​
3. 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.
4. Cagle P, et al. Lung Cancer Biomarkers: Present Status and Future Developments. Archives Pathology Lab Med. 2013;137:1191-1198.​​
5. 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.​
6. 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. ​
7. 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.
8. 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.​

US-90204 Last Updated 06/24

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FAQ

What were the key findings of the LAURA Phase III trial for TAGRISSO (AZN)?

TAGRISSO reduced the risk of disease progression or death by 84% compared to placebo in patients with unresectable, Stage III EGFR-mutated lung cancer.

How long was the median progression-free survival for TAGRISSO (AZN) in the Phase III LAURA trial?

The median progression-free survival was 39.1 months for TAGRISSO compared to 5.6 months for placebo.

Were there any new safety concerns identified in the LAURA Phase III trial for TAGRISSO (AZN)?

No new safety concerns were identified; however, Grade 3 or higher adverse events occurred in 35% of the TAGRISSO arm.

What was the overall survival trend in the LAURA Phase III trial for TAGRISSO (AZN)?

A favorable trend in overall survival was observed for TAGRISSO, but the data were not mature at the time of analysis.

In how many countries is TAGRISSO (AZN) approved?

TAGRISSO is approved in over 100 countries for various indications.

What specific patient subgroup benefits from TAGRISSO (AZN) in the LAURA Phase III trial?

Patients with unresectable, Stage III EGFR-mutated non-small cell lung cancer benefit from TAGRISSO.

What are some adverse effects associated with TAGRISSO (AZN) as reported in the LAURA Phase III trial?

Adverse effects include interstitial lung disease, QTc interval prolongation, cardiomyopathy, and other severe conditions.

What is the significance of the LAURA Phase III trial results for TAGRISSO (AZN)?

The trial results are significant as TAGRISSO is the first EGFR inhibitor to show benefit in the Stage III setting, potentially becoming the new standard of care.