3 March 2025
Imfinzi-based
perioperative regimen recommended for approval
in the EU by CHMP for resectable
non-small cell lung cancer
Recommendation based on AEGEAN Phase III trial
results
which showed Imfinzi reduced the risk of
recurrence, progression
or death by 32% vs. neoadjuvant chemotherapy
alone
AstraZeneca's Imfinzi (durvalumab) in combination
with chemotherapy has been recommended for approval in the European
Union (EU) for the treatment of adults with resectable non-small
cell lung cancer (NSCLC) at high risk of recurrence and no
epidermal growth factor receptor (EGFR) mutations or anaplastic
lymphoma kinase (ALK) rearrangements. In this regimen, patients are
treated with Imfinzi in
combination with neoadjuvant chemotherapy before surgery and as
adjuvant monotherapy after surgery.
The Committee for Medicinal Products for Human
Use (CHMP) of the European Medicines Agency (EMA) based its
positive opinion on results from the pivotal
AEGEAN trial, which were published in The New England Journal of
Medicine.
Results from a planned interim analysis of
event-free survival (EFS) showed a statistically significant and
clinically meaningful 32% reduction in the risk of recurrence,
progression events or death versus neoadjuvant chemotherapy alone
in patients treated with the Imfinzi-based perioperative regimen
(32% data maturity; EFS hazard ratio [HR] 0.68; 95% confidence
interval [CI] 0.53-0.88; p=0.003902). In a final analysis of
pathologic complete response (pCR), treatment with Imfinzi 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).
Additionally, interim overall survival (OS)
results presented at the 2024 World Conference on Lung Cancer
showed a favourable trend with the Imfinzi-based perioperative regimen
(35% data maturity; median OS: not reached [NR] versus
53.2 months; HR=0.89; 95% CI 0.70-1.14). The OS data
were not tested for statistical significance at this interim
analysis and will continue to be assessed as a key secondary
endpoint at final analysis.
Professor Martin Reck, Head of
the Department of Thoracic Oncology at the Lung Clinic
Grosshansdorf, Germany, member of the AEGEAN Steering
Committee and investigator in the trial, said: "Adding
perioperative durvalumab to neoadjuvant chemotherapy significantly
improved outcomes for patients with resectable non-small cell lung
cancer, who experience high rates of recurrence and poor outcomes.
Today's recommendation marks an important step towards patients and
their clinicians in Europe gaining access to an innovative
treatment that should become a backbone combination approach in
this curative-intent setting."
Susan Galbraith, Executive Vice President,
Oncology Haematology R&D, AstraZeneca, said: "This
recommendation highlights the potential of Imfinzi to address an unmet need for
patients with resectable lung cancer who need new treatment options
that increase the time they live without recurrence or progression.
AEGEAN underscores our commitment to transforming care in the early
stages of lung cancer where there is the greatest potential for
cure."
Each year in Europe, there are more than
450,000 people diagnosed with lung cancer.1 Around
25-30% of all patients with NSCLC, the most common form of lung
cancer, are diagnosed early enough to have surgery with curative
intent.2-3 However, the majority of patients with
resectable disease will develop recurrence and only 36-46% of
patients with Stage II disease will survive for five
years.4-5 This decreases to 24% for patients with Stage
IIIA disease and 9% for patients with Stage IIIB disease,
reflecting a high unmet medical need.4
Imfinzi was
generally well tolerated, and no new safety signals were observed
in the neoadjuvant and adjuvant settings. Further, adding
Imfinzi to neoadjuvant
chemotherapy was consistent with the known profile for this
combination and did not compromise patients' ability to complete
surgery versus chemotherapy alone.
Imfinzi is approved
in the US and several other countries in this setting based on the
AEGEAN results. Regulatory applications are also currently under
review in China, Japan and additional countries.
Imfinzi is the
global standard of care based on OS in the curative-intent setting
of unresectable, Stage III NSCLC in patients whose disease has not
progressed after chemoradiotherapy (CRT) based on the PACIFIC Phase
III trial.
Notes
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.6-7 Lung cancer is broadly split into
NSCLC and small cell lung cancer (SCLC), with 80-85% of patients
diagnosed with NSCLC.8-9 An
estimated 28,000 people are treated for resectable NSCLC across the
five major European countries each year.10
Early-stage lung cancer diagnoses are often
only made when the cancer is found on imaging for an unrelated
condition.11-12 The majority of patients with resectable
disease eventually develop recurrence despite complete tumour
resection and adjuvant chemotherapy.5
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. Perioperative therapy includes
treatment before and after surgery, also known as
neoadjuvant/adjuvant therapy. 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. Patients with known EGFR or
ALK genomic tumour aberrations were excluded from the primary
efficacy analyses.
In the AEGEAN trial, the primary endpoints were
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, defined as
residual viable tumour of less than or equal to 10% in the resected
primary tumour following neoadjuvant therapy, disease-free
survival, 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. The trial enrolled participants from 264 centres in more
than 25 countries including in the US, Canada, Europe, South
America 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 indications in
resectable, early-stage (IIa-IIIB) NSCLC and unresectable, Stage
III NSCLC, Imfinzi is
also approved for use in combination with a short course of
Imjudo (tremelimumab) and
chemotherapy for the treatment of metastatic
NSCLC. Imfinzi is also
approved for limited-stage small cell lung cancer (SCLC) in
patients whose disease has not progressed following concurrent
platinum-based CRT; and in combination with chemotherapy (etoposide
and either carboplatin or cisplatin) for the treatment of
extensive-stage SCLC.
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.
Contacts
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References
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Adrian Kemp
Company Secretary
AstraZeneca PLC
