Updated results from the CASPIAN Phase III trial showed AstraZeneca's Imfinzi (durvalumab) in combination with a choice of chemotherapies, etoposide plus either carboplatin or cisplatin, demonstrated a sustained, clinically meaningful overall survival (OS) benefit at three years for adults with extensive-stage small cell lung cancer (ES-SCLC) treated in the 1st-line setting.

These data, which show the longest survival update ever reported for an immunotherapy treatment in this setting, were presented during a mini-oral session on 18 September 2021 at the European Society of Medical Oncology (ESMO) Congress 2021.

The CASPIAN trial met the primary endpoint of OS in June 2019 (https://www.astrazeneca.com/media-centre/press-releases/2019/imfinzi-improves-overall-survival-at-interim-analysis-in-the-phase-iii-caspian-trial-in-1st-line-extensive-stage-small-cell-lung-cancer-27062019.html), reducing the risk of death by 27% (based on a hazard ratio [HR] of 0.73; 95% confidence interval [CI] 0.59-0.91; p=0.0047), which has formed the basis of regulatory approvals in many countries around the world. Updated results were previously presented during the ASCO20 Virtual Scientific Program in May 2020 (https://www.astrazeneca.com/media-centre/press-releases/2020/imfinzi-showed-a-sustained-overall-survival-benefit-in-1st-line-extensive-stage-small-cell-lung-cancer-in-the-phase-iii-caspian-trial.html) with a median follow up of more than two years.

The latest results for Imfinzi plus chemotherapy showed sustained efficacy after a median follow up of more than three years for censored patients, with a 29% reduction in the risk of death versus chemotherapy alone (based on an HR of 0.71; 95% CI 0.60-0.86; nominal p=0.0003). Updated median OS was 12.9 months versus 10.5 for chemotherapy.

The results included a planned exploratory analysis, where an estimated 17.6% of patients treated with Imfinzi plus chemotherapy were alive at three years, versus 5.8% of patients treated with chemotherapy alone. The survival benefits were consistent across all subgroups, in line with previous analyses.

Luis Paz-Ares, MD, PhD, Chair, Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain and principal investigator in the CASPIAN Phase III trial said: "Patients with extensive-stage small cell lung cancer historically have had limited treatment options and still face a dire prognosis, which makes these data showing that three times as many patients survive three years following Imfinzi treatment especially meaningful. These results reinforce Imfinzi plus platinum chemotherapy as an important standard of care in this setting."

Susan Galbraith, Executive Vice President, Oncology R&D, said: "This remarkable improvement in survival is an unprecedented achievement at three years for patients with extensive-stage small cell lung cancer. We are deeply committed to helping improve survival rates in this disease with research into new treatment options to transform outcomes at various stages, not only with the CASPIAN trial, but also with the ADRIATIC trial in limited-stage disease."

Imfinzi plus chemotherapy continued to demonstrate a well-tolerated safety profile consistent with the known profiles of these medicines. Results showed 32.5% of patients experienced a serious adverse event (all causality) with Imfinzi plus chemotherapy versus 36.5% with chemotherapy alone.

Imfinzi in combination with etoposide and either carboplatin or cisplatin is approved in the 1st-line setting of ES-SCLC in more than 55 countries, including the US, Japan, China and across the EU.

Imfinzi is also being tested following concurrent chemoradiation therapy (CRT) in patients with limited-stage SCLC in the ADRIATIC Phase III trial as part of a broad development programme. In addition, Imfinzi is also approved to treat non-small cell lung cancer (NSCLC) in the curative-intent setting of unresectable, Stage III disease after CRT in the US, Japan, China, across the EU and in many other countries, based on results from the PACIFIC Phase III trial.

Small cell lung cancer

Lung cancer is the leading cause of cancer death among men and women and accounts for about one-fifth of all cancer deaths.[1] Lung cancer is broadly split into NSCLC and SCLC, with about 15% classified as SCLC.[2]

SCLC is a highly aggressive, fast-growing form of lung cancer that typically recurs and progresses rapidly despite initial response to chemotherapy.[3,4] About two-thirds of SCLC patients are diagnosed with extensive-stage disease, in which the cancer has spread widely through the lung or to other parts of the body.[5 ]

Prognosis is particularly poor, as prior to the approval of immunotherapy regimens for ES-SCLC, only 7% of all patients with SCLC and only 3% of patients with extensive-stage disease will be alive five years after diagnosis.[5 ]

CASPIAN

CASPIAN was a randomised, open-label, multi-centre, global Phase III trial in the 1st-line treatment of 805 patients with ES-SCLC. The trial compared Imfinzi in combination with chemotherapy (etoposide and either carboplatin or cisplatin), or Imfinzi and chemotherapy with the addition of a second immunotherapy, tremelimumab, versus chemotherapy alone.

In the two experimental arms, patients were treated with four cycles of chemotherapy. In comparison, the control arm allowed up to six cycles of chemotherapy and optional prophylactic cranial irradiation.

The trial was conducted in more than 200 centres across 23 countries, including the US, Europe, South America, Asia and the Middle East. The primary endpoint was OS in each of the two experimental arms.

In June 2019, AstraZeneca announced the CASPIAN Phase III trial had met one primary endpoint of demonstrating OS for Imfinzi plus chemotherapy at a planned interim analysis. In March 2020, however, it was announced that the second experimental arm with tremelimumab did not meet its primary endpoint of OS.

Imfinzi

Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.

In addition to approvals in ES-SCLC and unresectable, Stage III NSCLC, Imfinzi is approved for previously treated patients with advanced bladder cancer in several countries. Since the first approval in May 2017, more than 100,000 patients have been treated with Imfinzi.

As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with NSCLC, SCLC, bladder cancer, hepatocellular carcinoma, biliary tract cancer (a form of liver cancer), oesophageal cancer, gastric and gastroesophageal cancer, cervical cancer, ovarian cancer, endometrial cancer, and other solid tumours.

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 (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and 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 immunotherapy

Immunotherapy is a therapeutic approach designed to stimulate the body's immune system to attack tumours. The Company's IO portfolio is anchored in immunotherapies that have been designed to overcome anti-tumour immune suppression. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumour types.

The Company is pursuing a comprehensive clinical-trial programme that includes Imfinzi as a single treatment and in combination with tremelimumab and other novel antibodies in multiple tumour types, stages of disease, and lines of treatment, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine the IO portfolio with radiation, chemotherapy, small, targeted molecules from across AstraZeneca's oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

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 (https://www.astrazeneca.com/) and follow the Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca).

Contacts

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References

1. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed September 2021.

2. LUNGevity Foundation. Types of Lung Cancer. Available at https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer. Accessed September 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 September 2021.

4. Kalemkerian GP, et al. Treatment Options for Relapsed Small-Cell Lung Cancer: What Progress Have We Made? JCO Oncol Pract. 2018;14:369-370.

5. Cancer.Net. Lung Cancer - Small Cell. Available at https://www.cancer.net/cancer-types/33776/view-all. Accessed September 2021.