AstraZeneca: ASTRAZENECA SECURES LICENSE EXTENSION AND EARLY NHS ENGLAND ACCESS TO TAGRISSO - (osimertinib) FOR PATIENTS WITH COMPLETELY RESECTED EARLY-STAGE EGFR MUTATION-POSITIVE NON-SMALL CELL LUNG CANCER

• This is the first authorisation to be issued by the MHRA under Project Orbis.¹
• AstraZeneca, NHS England and NICE have reached an agreement to enable early access to osimertinib for patients with this type of cancer, while NICE undertakes its appraisal.
• Patients with early-stage lung cancer are treated with the intention of cure; however, many relapse because treatment is limited to surgery and adjuvant chemotherapy.²
• Unprecedented clinical trial data show that osimertinib, the first approved targeted oral therapy in this setting, can reduce the risk of disease recurrence or death by 80% in patients with early-stage (IB-IIIA) EGFR mutation-positive NSCLC versus placebo.³

AstraZeneca today announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted a license extension for Tagrisso (osimertinib) in Great Britain, for use as monotherapy for the adjuvant treatment after complete tumour resection in adult patients with stage IB-IIIA non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations.⁴ This is the first authorisation to be issued by the MHRA under Project Orbis, a collaborative, global programme designed to deliver faster patient access to innovative cancer treatments.¹

An agreement with NHS England and the National Institute for Health and Care Excellence (NICE) will enable early access to osimertinib for all patients in England with this specific type of lung cancer. Access is given ahead of official NICE guidance to ensure patients have the chance to benefit from this new treatment option as soon as possible. NICE guidance is not expected to be published until September 2021 at the earliest.⁵

Dr Carles Escriu, Consultant in Thoracic Medical Oncology at The Clatterbridge Cancer Centre NHS Foundation Trust in Liverpool, said: "Today's news is potentially practice-changing because, for the first time, we have access to a targeted treatment for early-stage lung cancer. Osimertinib is a well-tolerated, once-daily tablet treatment and data show that, when taken after surgery, it can reduce the risk of disease recurrence or death by 80% after two years of treatment in patients with Stage IB-IIIA non-small cell lung cancer who have an EGFR mutation. Early-stage lung cancer patients can now be tested for EGFR mutations to give them the chance of delaying the return of cancer after surgery."

Arun Krishna, Head of Oncology, AstraZeneca UK, said: "Patients diagnosed in the earlier stages of EGFR mutation-positive non-small cell lung cancer have the best chance of living disease-free, but many see their cancer return. Osimertinib, which was discovered by AstraZeneca scientists in the UK, could significantly improve patient outcomes in a disease setting that has had no new treatment options in over a decade. With this in mind, we have worked with urgency to secure the MHRA license and access in England to bring this treatment option to patients as quickly as possible. We will continue to work with authorities in the other nations of the UK to secure patient access at the earliest opportunity."

The standard of care for patients with early-stage lung cancer is surgery with curative intent, followed by adjuvant chemotherapy in appropriate patients. Despite this, disease recurrence within five years of surgery remains high, and has been reported to occur in 45% of Stage IB, 62% of Stage II, and 76% of Stage III patients.²

In the ADAURA Phase III trial, adjuvant treatment (after surgery) with osimertinib in patients with stage II-IIIA EGFR mutation-positive NSCLC reduced the relative risk of disease recurrence or death by 83% compared to placebo (HR 0.17; 99.06% CI, 0.11 to 0.26; P<0.0011).³ When looking at the broader group of patients (stage IB-IIIA) a secondary endpoint treatment with osimertinib reduced the relative risk of disease recurrence or death by 80% compared to placebo, after 24 months of treatment (HR 0.20; 99.12% CI: 0.14, 0.30; P<0.001).³

Data from ADAURA also show that, at two years in patients with stage IB-IIIA disease, 89% of patients treated with osimertinib after surgery remained alive and disease-free versus 52% on placebo.³

Across the ADAURA, FLAURA and AURA studies for osimertinib, very common adverse reactions included: diarrhoea (47% all grades; 1.4% grade 3), stomatitis (24% all grades; 0.5% grade 3), rash (45% all grades; 0.7% grade 3), dry skin (32% all grades; 0.1% grade 3), paronychia (33% all grades; 0.4% grade 3), pruritus (17% all grades; 0.1% grade 3), platelet count decreased (53% all grades; 1.2% grade 3), leucocytes decreased (65% all grades; 1.2% grade 3), lymphocytes decreased (62% all grades; 6.1% grade 3) and neutrophils decreased (33% all grades; 3.2% grade 3).⁴ Common adverse reactions included: epistaxis (5.3% all grades; 0 grade 3), interstitial lung disease (3.7% all grades; 1.1% grade 3), Palmar-plantar erythrodysaesthesia syndrome (1.7% all grades; 0 grade 3), alopecia (4.6% all grades; 0 grade 3), urticaria (1.9% all grades; 0.1% grade 3) and blood creatinine increased (9.4% all grades; 0 grade 3).⁴

NOTES TO EDITORS

About osimertinib

In addition to the license extension announced today, osimertinib is also licensed in the United Kingdom as:

• monotherapy for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with activating EGFR mutations;
• and for the treatment of adult patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC.⁴

Osimertinib was discovered and developed in the UK by AstraZeneca scientists. It is a third generation, orally-administered EGFR TKI, a targeted therapy for advanced EGFR mutation-positive NSCLC.

In normal cells, EGFR plays a central role in regulating cell division and death; however, mutations in the EGFR can cause excessive cell growth and division. Osimertinib works by binding to the mutated EGFR thereby blocking the cell signalling pathway that drives the growth of tumour cells in NSCLC.⁶

For more information about osimertinib, a summary of product characteristics (SMPC) can be found here: https://www.medicines.org.uk/emc/product/1985/smpc. An updated version of the SMPC, which includes the license extension, is available upon request.

ADAURA

The license for osimertinib in early-stage NSCLC is based on data from ADAURA a randomised, double-blind, global, placebo-controlled Phase III trial in the adjuvant treatment of 682 patients with Stage IB, II and IIIA EGFR mutation-positive NSCLC following complete tumour resection and adjuvant chemotherapy as indicated. Patients were treated with osimertinib 80mg once-daily oral tablets or placebo for three years or until disease recurrence.

The trial enrolled patients in more than 200 centres across more than 20 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint was DFS in Stage II and IIIA patients and a key secondary endpoint was DFS in Stage IB, II and IIIA patients.

The data readout was originally anticipated in 2022. In April 2020, an Independent Data Monitoring Committee recommended for the trial to be unblinded two years early based on a determination of overwhelming efficacy. Investigators and patients continue to participate and remain blinded to treatment. The trial will continue to assess overall survival.

About lung cancer

Lung cancer is the most common cause of cancer death in the UK, accounting for one in five (21%) of all cancer deaths.⁷ NSCLC is the most common type more than 32,000 people in England are diagnosed with NSCLC every year,⁸ with around 12% having tumours with EGFR mutations.⁹ These patients are particularly sensitive to treatment with EGFR-tyrosine kinase inhibitors (TKIs) which block the cell-signalling pathways that drive the growth of tumour cells.⁶ Approximately 25-30% of patients with NSCLC present with resectable disease at diagnosis.^10,11,12

The UK has one of the worst five-year survival rates for lung cancer in Europe.¹³

AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas Oncology, Cardiovascular, Renal Metabolism, and Respiratory Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.

AstraZeneca is based in five different locations across the UK, with its global headquarters in Cambridge. In the UK, around 8,300 employees work in research and development, manufacturing, supply, sales and marketing. We supply 40 different medicines to the NHS. The UK is also an important location for AstraZeneca's clinical trials; in 2018, we undertook 201 trials in the UK, involving 376 centres and over 7,000 patients.

For more information, please visit www.astrazeneca.co.uk and follow us on Twitter @AstraZenecaUK.

References

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2. Pignon JP, Tribodet H, Scagliotti GV, et al. Lung Adjuvant Cisplatin Evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26:3552-3559.
3. Wu YL, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383:1711-1723.
4. Tagrisso (osimertinib). Summary of Product Characteristics. 1 October 2020. Available at: https://www.medicines.org.uk/emc/product/1985/smpcgref. Last accessed: May 2021
5. NICE. Osimertinib for adjuvant treatment of EGFR mutation-positive non-small-cell lung cancer after complete tumour resection [ID3835]. Project information. Available at: https://www.nice.org.uk/guidance/indevelopment/gid-ta10756. Last accessed: May 2021
6. Cross DA, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014;4:1046-1061.
7. Cancer Research UK. Lung cancer mortality statistics. Available at: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer/mortalityheading-Zero Last accessed May 2021.
8. Royal College of Physicians. National Lung Cancer Audit 2017 information sheet. Published January 2018. Available at: https://www.rcplondon.ac.uk/file/8703/download?token=2UCmNec9 Last accessed May 2021.
9. Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res. 2015;5;2892-2911.
10. Cagle PT, Allen TC, Olsen RJ. Lung cancer biomarkers: present status and future developments. Arch Pathol Lab Med. 2013;137:1191-1198.
11. Datta D, Lahiri B. Preoperative evaluation of patients undergoing lung resection surgery. Chest. 2003;123:2096-2103.
12. Le Chevalier T. Adjuvant chemotherapy for resectable non-small-cell lung cancer: where is it going? Ann Oncol. 2010;21:196-198.
13. Allemani C, et al. Global surveillance of trends in cancer survival: analysis of individual records for 37,513,025 patients diagnosed with one of 18 cancers during 2000-2014 from 322 population-based registries in 71 countries (CONCORD-3). Lancet. 2018 March 17; 391(10125): 1023-1075. doi:10.1016/S0140-6736(17)33326-3.

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Contacts:

UK Media Enquiries
Elisa Agate, AstraZeneca: 07780 493687 [e-mail]
Alex Larkinson, Edelman: 07980 687255 [e-mail]