3 February 2025
Imfinzi recommended for approval in the EU by CHMP as first and only
immunotherapy for limited-stage small cell lung
cancer
Recommendation based on
ADRIATIC Phase III trial results
which
showed
a 27% reduction in the risk of death versus
placebo
AstraZeneca's Imfinzi (durvalumab) has been
recommended for approval in the European Union (EU) as monotherapy
for the treatment of adults with limited-stage small cell lung
cancer (LS-SCLC) whose disease has not progressed following
platinum-based chemoradiation therapy (CRT).
The Committee for Medicinal Products
for Human Use (CHMP) of the European Medicines Agency (EMA) based
its positive opinion on the results from the
ADRIATIC Phase III trial, which
were published in The New England Journal of
Medicine.
Results showed Imfinzi reduced the risk of death
by 27% versus placebo (based on an overall survival [OS] hazard
ratio [HR] of 0.73; 95% confidence interval [CI] 0.57-0.93;
p=0.0104). Estimated median OS was 55.9 months for Imfinzi versus 33.4 months for
placebo. An estimated 57% of patients treated with Imfinzi were alive at three years
compared to 48% for placebo.
Imfinzi also reduced the risk
of disease progression or death by 24% (based on a progression-free
survival [PFS] HR of 0.76; 95% CI 0.61-0.95; p=0.0161) versus
placebo. Median PFS was 16.6 months for Imfinzi versus 9.2 months for placebo.
An estimated 46% of patients treated with Imfinzi had not experienced disease
progression at two years compared to 34% for placebo.
SCLC is a highly aggressive form of
lung cancer.1 LS-SCLC typically recurs and progresses
rapidly, despite initial response to standard-of-care chemotherapy
and radiotherapy.2-3 The prognosis for LS-SCLC is
particularly poor, as only 15-30% of patients will be alive five
years after diagnosis.4
Suresh Senan, PhD, Professor of
Clinical Experimental Radiotherapy at the Amsterdam University
Medical Centers, The Netherlands, and principal investigator in the
trial, said: "ADRIATIC was the first Phase III trial in decades to
demonstrate a survival benefit in limited-stage small cell lung
cancer, reducing the risk of death by 27 per cent in patients
treated with durvalumab versus placebo. Today's positive
recommendation from the CHMP means that our patients in Europe are
one step closer to gaining access to this practice-changing
treatment regimen."
Susan Galbraith, Executive Vice
President, Oncology Haematology, R&D, AstraZeneca, said: "With
57 per cent of patients still alive at three years in the ADRIATIC
trial, Imfinzi has the
potential to transform treatment for people with limited-stage
small cell lung cancer. If approved, these
patients will have access to immunotherapy for the first time,
redefining expectations of survival outcomes in this
setting."
The safety profile for Imfinzi was generally manageable and
consistent with the known profile of this medicine. No new safety
signals were observed.
Imfinzi is approved in the US
and several other countries in this setting based on the ADRIATIC
results. Regulatory applications are currently under review in
Japan and several other countries in this indication.
Notes
Small cell 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.5-6 Lung cancer is
broadly split into non-small cell lung cancer (NSCLC) and SCLC,
with about 15% of cases classified as SCLC.7
LS-SCLC (Stage I-III) is classified
as SCLC that is generally only in one lung or one side of the
chest.8 LS-SCLC accounts for approximately 30% of SCLC
diagnoses, with an estimated 8,000 people
treated for LS-SCLC across the five major European countries each
year.9-10 The prognosis for
patients with LS-SCLC remains poor despite curative-intent
treatment with standard-of-care concurrent CRT
(cCRT).9
ADRIATIC
The ADRIATIC trial is a randomised,
double-blind, placebo-controlled, multi-centre global Phase III
trial evaluating Imfinzi
monotherapy and Imfinzi
plus Imjudo (tremelimumab)
versus placebo in the treatment of 730 patients with LS-SCLC who
had not progressed following cCRT. In the experimental arms,
patients were randomised to receive a 1500mg fixed dose of
Imfinzi with or without
Imjudo 75mg every four
weeks for up to four doses/cycles each, followed by Imfinzi every four weeks for up to 24
months.
The dual primary endpoints were PFS
and OS for Imfinzi
monotherapy versus placebo. Key secondary endpoints included OS and
PFS for Imfinzi plus
Imjudo versus placebo,
safety and quality of life measures. The trial included 164 centres
in 19 countries across North and South America, Europe and
Asia.
Imfinzi
Imfinzi (durvalumab) is a human
monoclonal antibody that binds to the PD-L1 protein and blocks the
interaction of PD-L1 with the PD-1 and CD80 proteins, countering
the tumour's immune-evading tactics and releasing the inhibition of
immune responses.
In addition to its indication in
LS-SCLC, Imfinzi is the
only approved immunotherapy and the global standard of care in the
curative-intent setting of unresectable, Stage III NSCLC in
patients whose disease has not progressed after CRT. Additionally,
Imfinzi is approved as a
perioperative treatment in combination with neoadjuvant
chemotherapy in resectable NSCLC; in combination with chemotherapy
(etoposide and either carboplatin or cisplatin) for the treatment
of extensive-stage SCLC; and in combination with a short course of
Imjudo and chemotherapy
for the treatment of metastatic NSCLC.
Imfinzi is also approved in
combination with chemotherapy (gemcitabine plus cisplatin) in
locally advanced or metastatic biliary tract cancer and in
combination with Imjudo in
unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a
monotherapy in unresectable HCC in Japan and the EU.
Imfinzi is also approved in
combination with chemotherapy (carboplatin and paclitaxel) followed
by Imfinzi monotherapy in
primary advanced or recurrent endometrial cancer that is mismatch
repair deficient (dMMR) in the US. In the EU, Imfinzi plus chemotherapy followed by
Lynparza (olaparib) and
Imfinzi is approved for
patients with mismatch repair proficient (pMMR) advanced or
recurrent endometrial cancer, and Imfinzi plus chemotherapy followed by
Imfinzi alone is approved
for patients with dMMR disease. In Japan, Imfinzi plus chemotherapy followed by
Imfinzi monotherapy has
also been approved as 1st-line treatment in primary advanced or
recurrent endometrial cancer, and Imfinzi plus chemotherapy followed by
Imfinzi and Lynparza has been approved for
patients with pMMR disease.
Since the first approval in May
2017, more than 374,000 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 SCLC, NSCLC, bladder cancer, breast cancer, several
gastrointestinal and gynaecologic cancers, 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 and Imjudo; Enhertu (trastuzumab deruxtecan) and
Datroway (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 immuno-oncology (IO)
AstraZeneca is a pioneer in
introducing the concept of immunotherapy into dedicated clinical
areas of high unmet medical need. The Company has a comprehensive
and diverse IO portfolio and pipeline anchored in immunotherapies
designed to overcome evasion of the anti-tumour immune response and
stimulate the body's immune system to attack tumours.
AstraZeneca strives to redefine
cancer care and help transform outcomes for patients with
Imfinzi as a monotherapy
and in combination with Imjudo as well as other novel
immunotherapies and modalities. The Company is also investigating
next-generation immunotherapies like bispecific antibodies and
therapeutics that harness different aspects of immunity to target
cancer, including cell therapy and T-cell engagers.
AstraZeneca is pursuing an
innovative clinical strategy to bring IO-based therapies that
deliver long-term survival to new settings across a wide range of
cancer types. The Company is focused on exploring novel combination
approaches to help prevent treatment resistance and drive longer
immune responses. With an extensive clinical programme, the Company
also champions the use of IO treatment in earlier disease stages,
where there is the greatest potential for cure.
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's innovative
medicines are sold in more than 125 countries and used by millions
of patients worldwide. Please visit astrazeneca.com and
follow the Company on social media @AstraZeneca.
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References
1. 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 February 2025.
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Small-Cell Lung Cancer: What Progress Have We
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3. Cheng Y, et al. Durvalumab after Chemoradiotherapy in
Limited-Stage Small-Cell Lung Cancer. N Engl J
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4. Bebb DG, et al. Symptoms and Experiences with Small Cell Lung
Cancer: A Mixed Methods Study of Patients and
Caregivers. Pulm
Ther. 2023;9:435-450.
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https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf.
Accessed February 2025.
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on Cancer. World Fact Sheet. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf.
Accessed February 2025.
7. LUNGevity Foundation. Types of Lung Cancer. Available
at:
https://www.lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed February 2025.
8. American Cancer Society. Small Cell Lung Cancer Stages.
Available at:
https://www.cancer.org/cancer/types/lung-cancer/detection-diagnosis-staging/staging-sclc.html. Accessed
February 2025.
9. Senan S, et al. ADRIATIC: A phase III trial of durvalumab ±
tremelimumab after concurrent chemoradiation for patients with
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10. AstraZeneca PLC. Investor Relations Epidemiology Spreadsheet.
Available at: https://www.astrazeneca.com/investor-relations.html.
Accessed February 2025.
Adrian Kemp
Company Secretary
AstraZeneca PLC
