At the forefront of lung cancer treatment
Lung cancer is the leading cause of cancer death worldwide, accounting for about 2.2 million patients diagnosed and 1.8 million deaths each year.1 The two main types of lung cancer are non-small cell lung cancer (NSCLC), which represents 80-85% of patients, and small cell lung cancer (SCLC), the more aggressive and fast-growing cancer type representing about 15% of patients.2-3
The earlier we can detect and treat lung cancer, the closer we are to cure.4-5 Unfortunately, early diagnosis is not always a reality.6
In many cases, lung cancer goes undetected until it is in advanced stages or the cancer comes back after initial treatment.6 For these patients who experience recurrence, outcomes are especially poor.4-5 To meaningfully improve outcomes, we are prioritising lung cancer research to increase early screening and diagnosis and address the significant unmet need for treatments at every stage of the disease continuum.
Our approach
Our portfolio of approved and potential new medicines in late-stage development spans different histologies, several stages of disease, lines of therapy and modes of action.7 Our approach is driven by precision medicine, using groundbreaking science to further our understanding of lung cancer and deliver medicines matched to the patients who can best benefit from them. This includes thinking differently about the underlying biology of lung cancer, from early stages – where we aim to help patients live longer and cancer-free – to late stages, where we look to meaningfully extend survival.
Targeting Biomarkers and Resistance Mechanisms
By focusing on the unique properties of a tumour and looking in new places – beyond traditional classifications – we are defining new biomarkers and therapeutic targets to transform the way people with lung cancer are diagnosed and treated.
Our research has led us to address the unmet needs of patients with mutations in the epidermal growth factor receptor (EGFR), which occur in 10-15% of NSCLC patients in the US and EU, and 30-40% of NSCLC patients in Asia.8-10 We also partnered to launch the first tissue-based diagnostic and the first plasma-based (ctDNA) diagnostic to identify EGFR mutations (EGFRm) in NSCLC, both of which are used extensively in clinical practice.11-12 However, despite advances in testing and treatment, most patients with EGFRm NSCLC will develop resistance to treatment and progress to later stages of disease.13-14 We are improving our understanding of resistance mechanisms and emerging biomarkers, such as MET gene alterations, to help answer what comes next for patients whose cancer has progressed despite treatment with today’s standard-of-care therapies.
Human epidermal growth factor 2 (HER2) and TROP2 are two additional biomarkers we are actively researching as promising targets for precision medicine. Currently, patients whose tumours express HER2 or TROP2 and who have progressed after treatment have limited options, as there are no available HER2 or TROP2 directed medicines approved in NSCLC.15 We are investigating antibody drug conjugates (ADCs) to target actionable biomarkers such as HER2 and TROP2. Unlike conventional chemotherapy treatments which can damage healthy cells, ADCs can deliver a cancer drug directly into cancer cells to reduce damage caused to healthy cells.16
For those patients that we cannot serve with therapies targeted to an actionable mutation, our extensive late-stage Immuno-Oncology (IO) programme may provide clinical benefit.7
Boosting the Immune Response to Cancer
As we continue to advance science for NSCLC patients with an identifiable mutation, we are simultaneously ushering in a new era of care with our lmmuno-Oncology pipeline. Our immunotherapies have been designed to target immune checkpoints that are exploited by cancer to avoid or suppress the immune system’s ability to recognise and destroy cancer cells.17
Advancing Treatments with Cure in Mind
While many new treatments have focused on advancing care for metastatic patients with a high unmet medical need, we prioritised pushing treatment into earlier lung cancer settings. To really cure cancer, we need to treat earlier to maximise the potential for long-term disease remission and the possibility of cure.6 In pursuit of this goal, we have launched more than a dozen Phase II and III clinical trials evaluating our Immuno-Oncology and gene-targeted therapies in earlier stages of disease.7 In the Immuno-Oncology space alone, we now lead with the largest proportion of Phase III trials in early disease across the industry, with many ongoing across the NSCLC and SCLC settings.7
Key to improving survivorship are technologies that can identify cancer earlier, signal relapse earlier and target treatment regimens from the start.6 This includes investigating novel approaches to identify patients at risk of recurrence – such as monitoring for the presence of minimal residual disease (MRD) using ctDNA – so that physicians can intervene earlier and tailor the best treatment options for individual cancer patients.18
In order to realise the survivorship potential in early disease, we are strategically partnering with innovative organisations to leverage specialised technologies to optimise the use and impact of early regimens. These investments in non-invasive diagnostics and screening tools are part of our overall data-driven approach to help physicians intervene earlier with intelligently tailored treatment regimens that can deliver longer, quality survival for new groups of patients.
Changing the Pace of Progress in Lung Cancer Survival
We are proud to be a founding member of the Lung Ambition Alliance, a partnership of organisations with the ambitious but attainable goal to double five-year survival by 2025. To meet this goal, the Lung Ambition Alliance advocates for improved approaches in three key areas – increasing screening rates and diagnostic testing, accelerating the delivery of innovative medicine and improving quality of care. One of the Alliance’s flagship initiatives is the ILC2 grant program, which provides funding to help non-profit patient and caregiver organisations execute projects that have the potential to transform patient care. The Alliance is also helping to validate surrogate endpoints to accelerate drug approval in earlier settings of lung cancer and create a global registry of CT imaging data to enhance screening in early-stage lung cancer.19
Following the science in lung cancer
Join us
We are driven by our passion, our people and a culture of innovation. We value courage, curiosity, collaboration and passion for learning, and we encourage disruptive thinking where failure is an opportunity to learn – the freedom to take risks without fear of failure.
Our people
"I believe personalised healthcare is the future of medicine; it allows us to use the latest diagnostic science to target medicines to patients most likely to benefit." Ruth March, Senior Vice-President of Precision Medicine, R&D Oncology
References
1. World Health Organization. Globocan 2020 Fact Sheet. Available at: https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed January 2021.
2. American Cancer Society. What is Lung Cancer? Available at: http://www.cancer.org/cancer/lung-cancer/about/what-is.html. Accessed January 2021.
3. National Cancer Institute. NCI Dictionary - Small Cell Lung Cancer. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-cell-lung-cancer. Accessed January 2021.
4. ASCO. Lung Cancer - Small Cell. Available at: https://www.cancer.net/cancer-types/33776/view-all. Accessed January 2021.
5. ASCO. Lung Cancer - Non-Small Cell. Available at: https://www.cancer.net/cancer-types/lung-cancer/view-all. Accessed January 2021.
6. LUNGevity Foundation. Screening & Early Detection. Available at: https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection. Accessed January 2021.
7. AstraZeneca LLC. Clinical trials appendix - Year-to-date and Q3 2020 results update. Available at: https://www.astrazeneca.com/content/dam/az/PDF/2020/q3/Year-to-date_and_Q3_2020_results_clinical_trials_appendix.pdf. Accessed January 2021.
8. 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.
9. 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.
10. 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.
11. AstraZeneca LLC. AstraZeneca and Roche announce partnership to develop companion diagnostic test for AZD9291. Available at: https://www.astrazeneca.com/media-centre/press-releases/2014/astrazeneca-roche-azd9291-companion-diagnostic-test-lung-cancer-28072014.html#!. Accessed January 2021.
12. Siravegna G, et al. How Liquid Biopsies Can Change Clinical Practice in Oncology. Ann Oncol. 2019;30:1580-1590.
13. Yang CH, et al. Pemetrexed had Significantly Better Clinical Efficacy in Patients with Stage IV Lung Adenocarcinoma with Susceptible EGFR Mutations Receiving Platinum-based Chemotherapy after Developing Resistance to the First-line Gefitinib Treatment. Onco Targets Ther. 2016;9:1579-1587.
14. Morgillo F, et al. Mechanisms of Resistance to EGFR Targeted Drugs: Lung Cancer. ESMO Open. 2016;1:e000060.
15. Tsurutani J, et al. Targeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors. Cancer Discov. 2020;10(5):OF1-OF14.
16. Peters C, et al. Antibody-drug conjugates as novel anti-cancer chemotherapeutics. Biosci Rep. 2015;35(4):e00225.
17. American Cancer Society. Immune Checkpoint Inhibitors and Their Side Effects. Available at: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immune-checkpoint-inhibitors.html. Accessed January 2021.
18. National Cancer Institute. Minimal Residual Disease. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/minimal-residual-disease. Accessed January 2021.
19. Lung Ambition Alliance. Available at: https://www.lungambitionalliance.com/. Accessed January 2021.
Document ID: Z4-30404
Date of Preparation: January 2021