26 July 2024
FDA Advisory Committee
reviewed Imfinzi for
treatment of resectable non-small cell lung cancer based on AEGEAN
Phase III trial results
The Food and Drug Administration's (FDA)
Oncologic Drugs Advisory Committee (ODAC) acknowledged that
AstraZeneca's Imfinzi
(durvalumab) met the primary endpoint of event-free survival (EFS)
in the treatment of resectable non-small cell lung cancer (NSCLC)
based on the AEGEAN Phase III trial results with an overall
tolerable safety profile. In the trial, adult patients with
resectable early-stage (IIA-IIIB) NSCLC and no known epidermal
growth factor receptor (EGFR) mutations or anaplastic lymphoma
kinase (ALK) rearrangements were treated with Imfinzi in combination with
neoadjuvant chemotherapy before surgery and as adjuvant monotherapy
after surgery. The discussion noted that while the
contribution by phase of neoadjuvant and adjuvant components of the
perioperative regimen could not be clearly assigned based on the
trial design, this is an important potential regimen for
patients.
The FDA accepted the supplemental Biologics
License Application (sBLA) in September 2023 for Imfinzi in this indication based on
positive results from the pivotal
AEGEAN trial, which were published in
The New England
Journal of Medicine in October 2023.
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: "The majority of
patients with resectable lung cancer face recurrence of their
disease even after surgery and neoadjuvant chemotherapy. The
Committee acknowledged the potential to address this urgent unmet
need with durvalumab both before and after surgery, which can
significantly increase the time patients live without progression
and recurrence events in this curative-intent setting."
Susan Galbraith, Executive Vice President,
Oncology R&D, AstraZeneca, said: "The Committee's discussion of
the AEGEAN data highlighted the significant benefit delivered by
this Imfinzi-based regimen
for patients with resectable lung cancer. We are committed to
working closely with the FDA to bring this novel immunotherapy
option to patients that offers a flexible chemotherapy
backbone."
Results from a planned interim analysis of EFS
from the AEGEAN trial 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).
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.
The ODAC provides the FDA with independent,
expert advice and recommendations on marketed and investigational
medicines for use in the treatment of cancer. The FDA will consider
the feedback as it reviews the submission and is not bound by the
Committee's recommendation.
Imfinzi is
approved in Switzerland and the UK
for the treatment of adults with resectable NSCLC in Stage II
and III without known EGFR mutations or ALK rearrangements, based
on the AEGEAN results. Regulatory applications for Imfinzi in this setting are also
currently under review in the EU, China and several other
countries.
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
Each year, there are an estimated
2.4 million people diagnosed with lung cancer
globally.1 Lung cancer is the
leading cause of cancer death among both men and women, accounting
for about one-fifth of all cancer deaths.1-2 Lung cancer
is broadly split into NSCLC and small cell lung cancer (SCLC), with
80-85% of patients diagnosed with NSCLC.3-4
The majority of NSCLC patients are
diagnosed with advanced disease while approximately 25-30% present
with resectable disease at diagnosis.5-6 Early-stage
lung cancer diagnoses are often only made when the cancer is found
on imaging for an unrelated condition.7-8
The majority of patients with
resectable disease eventually develop recurrence despite complete
tumour resection and adjuvant chemotherapy.9
Only 36-46% of patients with Stage II
disease will survive for five years.10 This decreases to
24% for patients with Stage IIIA disease and 9% for patients with
Stage IIIB disease, reflecting a high unmet medical
need.10
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
and regions 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 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
1. World Health Organization. International Agency for Research
on Cancer. Lung Fact Sheet. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf.
Accessed July 2024.
2. World Health Organization. International Agency for Research
on Cancer. World Fact Sheet. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf.
Accessed July 2024.
3. LUNGevity Foundation. Types of Lung Cancer. Available
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https://www.lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed July 2024.
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https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection.
Accessed July 2024.
9. Pignon JP, et al.
Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE
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Adrian Kemp
Company Secretary
AstraZeneca
PLC