IMFINZI▼(DURVALUMAB) IN COMBINATION WITH CHEMOTHERAPY APPROVED IN GREAT BRITAIN FOR THE TREATMENT OF RESECTABLE NON-SMALL CELL LUNG CANCER

IMFINZI▼(DURVALUMAB) in combination with chemotherapy APPROVED IN GREAT BRITAIN for the treatment of resectable non-small cell lung cancer

• Today’s approval from the MHRA is based on positive data from the AEGEAN Phase III trial in resectable non-small cell lung cancer, which showed that Imfinzi (durvalumab)-based treatment before and after surgery reduced the risk of recurrence, progression events or death by 32% versus neoadjuvant chemotherapy alone.[1]
• This decision means that durvalumab is now licenced in Great Britain in both the resectable and unresectable non-small cell lung cancer settings which further reinforces AstraZeneca’s bold ambition to lead a revolution in oncology to redefine cancer care in the UK. [2]
• Lung cancer often goes undetected until it is in advanced stages and is the most common cause of cancer death in the UK, accounting for 21% of all cancer deaths.[3],[4] The UK has one of the worst five-year survival rates for lung cancer in Europe.⁴

London, UK, Tuesday 9 July 2024 – Today, AstraZeneca announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation in Great Britain for Imfinzi (durvalumab) in combination with platinum-based chemotherapy as a neoadjuvant treatment before surgery, followed by durvalumab as adjuvant monotherapy after surgery for the treatment of adults with resectable (tumours ≥4 cm and/or node positive) non-small cell lung cancer (rNSCLC) and no known epidermal growth factor receptor (EGFR) mutations or ALK rearrangements/aberrations.²

Following the European Commission (EC) decision in 2018 to approve durvalumab in adult patients with locally advanced, unresectable NSCLC whose tumours express PD-L1 on ≥ 1% of tumour cells and whose disease has not progressed following platinum based chemoradiation therapy, durvalumab is now licenced in Great Britain for both resectable and unresectable NSCLC.^2,[5]

Dr John Conibear, Clinical Director of Thoracic Oncology at Barts Cancer Centre, said: “This decision by the MHRA recognises an important clinical improvement in outcomes for patients with resectable non-small cell lung cancer (rNSCLC), where new options are urgently needed for long-term survival. Patients with rNSCLC still experience unacceptably high rates of disease recurrence within five years of surgery. Data from the AEGEAN Phase III trial has shown that durvalumab-based treatment before and after surgery significantly increased the time patients can live without recurrence or progression events.”

Lung cancer is the most common cause of cancer death in the UK, accounting for 21% of all cancer deaths.⁴ The UK has one of the worst five-year survival rates for lung cancer in Europe.⁴ Patients with rNSCLC still experience unacceptably high rates of disease recurrence within five years of surgery.[6] For patients who experience recurrence, outcomes are especially poor, therefore the earlier we detect and treat lung cancer, the more we can improve patient outcomes.^6,[7]

David Harland, Head of Oncology Medical Affairs, AstraZeneca UK, said: “Today’s important MHRA approval of durvalumab marks a major advancement and opens a new chapter in the treatment of resectable non-small cell lung cancer. This decision means that durvalumab is now approved in Great Britian in both resectable and unresectable NSCLC. We are committed to working with NICE and NHS England to ensure rapid access for patients.”

The decision from the MHRA was based on a planned interim analysis of event-free survival (EFS) from the AEGEAN Phase III trial, which showed that patients treated with durvalumab in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery achieved a 32% reduction in the risk of recurrence, progression events or death versus neoadjuvant chemotherapy alone (32% data maturity, EFS hazard ratio [HR] of 0.68, 95% confidence interval [CI] 0.53-0.88; p=0.004).¹ At 24 months, event-free survival was 63.3% in the durvalumab group (95% CI, 56.1 to 69.6) and 52.4% in the placebo group (95% CI, 45.4 to 59.0), providing an absolute risk reduction of 10.9%.1

In a final analysis of pathologic complete response (pCR), a dual primary endpoint, treatment with durvalumab plus neoadjuvant chemotherapy before surgery resulted in a pCR rate of 17.2% versus 4.3% for patients treated with neoadjuvant chemotherapy alone (difference in pCR 13.0%; 95% CI 8.7-17.6).¹

Durvalumab plus chemotherapy was generally well tolerated, and no new safety signals were observed in the neoadjuvant and adjuvant settings.¹ Adding durvalumab to neoadjuvant chemotherapy was consistent with the known safety profiles of the individual drugs and did not compromise patients' ability to complete surgery versus neoadjuvant chemotherapy alone.¹ Of patients treated with the durvalumab-based regimen, 77.6% completed surgery compared to 76.7% of patients treated with neoadjuvant chemotherapy alone.¹

Grade 3/4 any-cause adverse events occurred in 42.4% of patients treated with the durvalumab-based regimen versus 43.2% for neoadjuvant chemotherapy alone.¹ The most common adverse events of any cause largely reflected the safety profile of the chemotherapy agents used in the trial; the incidence of the most common adverse events was largely similar across both groups.¹

– ENDS –

CONTACTS

UK Media Enquiries

Emma White, AstraZeneca: 07385 516437 / emma.white1@astrazeneca.com

Jack Faulkner, Edelman: 07813 407324 / jack.faulkner@edelman.com 

NOTES TO EDITORS

About durvalumab

Durvalumab is a human monoclonal antibody that targets the programmed death ligand-1 (PD-L1), an important part of the mechanism that cancer cells use to hide from the body’s immune system. PD-L1 is expressed on T-cells and tumour cells.[8]^,[9] By selectively blocking PD-L1, durvalumab can enable the immune system to recognise and attack the cancer cell.^,

For complete information on durvalumab, the summary of product characteristics, including a full list of side effects and adverse reactions is available here: https://www.medicines.org.uk/emc/product/9495/smpc

About AEGEAN

AEGEAN is a randomised, double-blind, multi-centre, placebo-controlled global Phase III trial evaluating Imfinzi as perioperative treatment for patients with resectable Stage IIA-IIIB (Eighth Edition AJCC Cancer Staging Manual) NSCLC, irrespective of PD-L1 expression.[10] Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy.^1, In the trial, 802 patients were randomised to receive a 1500mg fixed dose of Imfinzi plus chemotherapy or placebo plus chemotherapy every three weeks for four cycles prior to surgery, followed by Imfinzi or placebo every four weeks (for up to 12 cycles) after surgery.¹ Patients with known EGFR or ALK genomic tumour aberrations were excluded from the primary efficacy analyses.

In the AEGEAN trial, the primary endpoints were pathologic complete response (pCR), defined as no viable tumour in the resection specimen (including lymph nodes) following neoadjuvant therapy, and EFS, defined as the time from randomisation to an event like tumour recurrence, progression precluding definitive surgery, or death. Key secondary endpoints were major pathologic response (mPR), defined as residual viable tumour of less than or equal to 10% in the resected primary tumour following neoadjuvant therapy, DFS, OS, safety and quality of life. The final pathologic response analyses were performed after all patients had the opportunity for surgery and pathology assessment per the trial protocol.¹ The trial enrolled participants in 225 centres including in the US, Canada, Europe, South America and Asia.^1,

About lung cancer

Lung cancer is the most common cause of cancer death in the UK, accounting for 21% of all cancer deaths.⁴ Lung cancer is broadly split into NSCLC and small cell lung cancer (SCLC), of which NSCLC is more common.[11] The majority of NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.[12]^,[13] Resectable lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.^3,[14]

AstraZeneca

AstraZeneca 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. AstraZeneca operates in over 100 countries and its medicines are used by millions of patients worldwide.

With a proud 100-year heritage in advancing UK science, today AstraZeneca is the UK’s leading biopharmaceutical company. The company is based in five different locations across the UK, with its global headquarters in Cambridge. In the UK, around 8,700 employees work in research and development, manufacturing, supply, sales, and marketing. We supply around 36 different medicines to the NHS.

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

References

[1] Heymach JV, et al. Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N Engl J Med. 2023;389(18):1672-1684.

[2] Electronic Medicines Compendium (EMC). Imfinzi 50 mg/mL concentrate for solution for infusion - Summary of Product Characteristics (SmPC). Available at: https://www.medicines.org.uk/emc/product/9495/smpc#gref. Last accessed: July 2024.

[3] LUNGevity Foundation. Screening & Early Detection. Available at: https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection. Last accessed: July 2024.

[4] Cancer Research UK. Lung Cancer Statistics. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer#heading-One. Last accessed: July 2024.

[5] European Medicines Agency. CHMP Summary of positive opinion for Imfinzi. Available at: https://www.ema.europa.eu/en/documents/smop-initial/chmp-summary-positive-opinion-imfinzi_en.pdf. Last accessed: July 2024.

[6] Uramoto H, Tanaka F. Recurrence after surgery in patients with NSCLC. Transl Lung Cancer Res. 2014;3(4):242-9.

[7] Ning J, Ge T, et al. Early diagnosis of lung cancer: which is the optimal choice? Aging (Albany NY). 2021;13(4):6214-6227.

[8] Stewart R, Morrow M, Hammond SA, et al. Identification and characterization of MEDI4736, an antagonistic anti–PD-L1 monoclonal antibody. Cancer Immunol Res. 2015;3:1052-1062.

[9] Patel S, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015;14:847-856.

[10] Clinicaltrials.gov. A Study of Neoadjuvant/​Adjuvant Durvalumab for the Treatment of Patients with Resectable Non-small Cell Lung Cancer (AEGEAN) - NCT03800134. Available at: https://clinicaltrials.gov/study/NCT03800134. Last accessed: July 2024.

[11] Cancer Research UK. Types of lung cancer. Available at: https://www.cancerresearchuk.org/about-cancer/lung-cancer/stages-types-grades/types. Last accessed: July 2024.

[12] Cagle PT, et al. Lung cancer biomarkers: present status and future developments. Arch Pathol Lab Med. 2013;137(9):1191-1198.

[13] Le Chevalier T. Adjuvant chemotherapy for resectable non-small-cell lung cancer: where is it going? Ann Oncol. 2010;21 Suppl 7:vii196-198.

[14] Sethi S, et al. Incidental Nodule Management – Should There Be a Formal Process? J Thorac Onc. 2016:8;S494-S497.