16 August 2024
Imfinzi approved in the US for the
treatment of resectable
non-small
cell lung cancer before and after surgery
Based on
AEGEAN Phase III trial results which showed Imfinzi-based regimen
reduced the risk of recurrence, progression or death by 32% vs.
neoadjuvant chemotherapy alone
AstraZeneca's Imfinzi (durvalumab) in combination
with chemotherapy has been approved in the US for the treatment of
adult patients with resectable early-stage (IIA-IIIB) non-small
cell lung cancer (NSCLC) and no known 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 approval by the Food and Drug
Administration (FDA) was based on positive results from the
pivotal
AEGEAN trial, which were
published in The New England Journal of
Medicine in October 2023.
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 chemotherapy alone in patients
treated with the Imfinzi-based regimen before and after
surgery (32% data maturity; EFS hazard ratio of 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).
Each year, there are an estimated
2.4 million people diagnosed with lung cancer globally, with
approximately 235,000 new diagnoses expected in the US in
2024.1-2 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.3-4 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.5-6 This decreases to 24% for patients with Stage
IIIA disease and 9% for patients with Stage IIIB disease,
reflecting a high unmet medical need.6
John V. Heymach, MD, PhD, Professor
and Chair Thoracic/Head and Neck Medical Oncology, The University
of Texas MD Anderson Cancer Center in Houston, Texas, said: "This
approval brings an important new treatment option that should
become a backbone combination approach for patients with resectable
non-small cell lung cancer, who have historically faced high rates
of recurrence even after chemotherapy and surgery. When added both
before and after surgery, durvalumab delivered a significant and
meaningful improvement in outcomes in this curative-intent
setting."
Dave Fredrickson, Executive Vice
President, Oncology Business Unit, AstraZeneca, said: "Today's
approval of Imfinzi in
resectable early-stage lung cancer builds on its strong foundation
of changing clinical practice in unresectable Stage III disease. We
remain committed to bringing novel approaches like AEGEAN to early
lung cancer settings where cure is the goal of
treatment."
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 also
approved in the UK,
Switzerland and Taiwan (China) in this setting based on the AEGEAN
results. Regulatory applications are also currently under review in
the EU, China and several other countries in this
indication.
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 chemoradiotherapy
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.1,7 Lung cancer is
broadly split into NSCLC and small cell lung cancer (SCLC), with
80-85% of patients diagnosed with NSCLC.8-9
Early-stage lung cancer diagnoses
are often only made when the cancer is found on imaging for an
unrelated condition.10-11 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, overall 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.
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 chemoradiotherapy.
Imfinzi in combination
with chemotherapy (etoposide and either carboplatin or cisplatin)
is also approved for the treatment of extensive-stage SCLC and in
combination with a short course of Imjudo (tremelimumab) and chemotherapy
for the treatment of metastatic NSCLC.
In limited-stage SCLC, Imfinzi demonstrated statistically
significant and clinically meaningful improvements in the dual
primary endpoints of OS and progression-free survival compared to
placebo in patients who had not progressed following
standard-of-care concurrent chemoradiotherapy in the ADRIATIC Phase
III trial.
In addition to its indications in
lung cancers, Imfinzi is
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 and in combination with chemotherapy (carboplatin plus
paclitaxel) followed by Imfinzi monotherapy in primary
advanced or recurrent endometrial cancer that is mismatch repair
deficient in the US.
Since the first approval in May
2017, more than 220,000 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, breast cancer, bladder 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
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
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Accessed August 2024.
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Accessed August 2024.
Adrian Kemp
Company Secretary
AstraZeneca PLC