TIDMAZN
RNS Number : 3943O
AstraZeneca PLC
29 May 2020
29 May 2020 13:00 BST
Imfinzi showed a sustained overall survival benefit in
1st-line
extensive-stage small cell lung cancer in the Phase III CASPIAN
trial
ASCO data show more than 10% of patients on Imfinzi plus
chemotherapy had not progressed and remained on treatment at two
years vs. 2.9% on chemotherapy alone
Detailed results from an updated analysis of the Phase III
CASPIAN 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 for adults with
extensive-stage small cell lung cancer (ES-SCLC) treated in the
1st-line setting.
The CASPIAN trial met the primary endpoint of OS in June 2019 ,
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
formed the basis of the US FDA approval in March 2020 .
After a median follow up of more than two years, the latest
results for Imfinzi plus chemotherapy showed sustained efficacy,
maintaining a 25% reduction in the risk of death versus
chemotherapy alone (based on an HR of 0.75; 95% CI 0.62, 0.91;
nominal p=0.0032). Updated median OS was 12.9 months versus 10.5
for chemotherapy. In a post-hoc analysis, an estimated 22.2% of
patients treated with Imfinzi plus chemotherapy were alive at 24
months versus 14.4% for chemotherapy.
For Imfinzi plus chemotherapy, 11% of patients were alive and
progression-free at 24 months versus 2.9% for chemotherapy alone
(post-hoc). Imfinzi plus chemotherapy maintained a high confirmed
objective response rate (ORR) (68% versus 58%) and in a post-hoc
analysis, duration of response (DoR) for Imfinzi at 24 months was
13.5% versus 3.9% for chemotherapy. At 24 months, 12% of patients
in the Imfinzi plus chemotherapy arm remained on Imfinzi
treatment.
Luis Paz-Ares MD, Ph.D., Chair, Medical Oncology Department,
Hospital Universitario Doce de Octubre, Madrid, Spain and principal
investigator in the Phase III CASPIAN trial said: "These updated
results from the CASPIAN trial show a remarkable 22% of patients
still alive at 24 months, supporting the sustained benefits of
treatment with Imfinzi plus chemotherapy. This is an effective
1st-line treatment in the extensive-stage setting, where improving
outcomes has been a challenge and so few patients survive five
years."
José Baselga, Executive Vice President, Oncology R&D, said:
"After two years median follow-up, Imfinzi continues to show
sustained and meaningful improvements in survival and prolonged
treatment response for patients facing this devastating and
aggressive disease. These data reinforce Imfinzi plus chemotherapy
as an important new standard of care for extensive-stage small cell
lung cancer patients, and this regimen offers patients convenient
dosing every four weeks during maintenance. We look forward to
bringing the benefits of Imfinzi to patients around the world."
The second experimental arm in the CASPIAN trial testing
tremelimumab, an anti-CTLA4 monoclonal antibody, added to Imfinzi
and chemotherapy showed a trend towards OS, but did not reach
statistical significance compared to chemotherapy alone.
Summary of updated results:
Data cut-off date was 27 January 2020. Formal statistical
analysis was completed at the time of the interim analysis per
trial protocol. Therefore, no formal testing for statistical
significance could be performed in this updated analysis.
EP(i) + Imfinzi EP(i)
(n=268) (n=269)
OS (primary endpoint)
------------------ --------------
Number of deaths 210 (78.4%) 231 (85.9%)
------------------ --------------
Hazard ratio 0.75 (0.62, 0.91)
------------------ --------------
Nominal p-value 0.0032
------------------ --------------
Median in months 12.9 10.5
(95% CI) (11.3, 14.7) (9.3, 11.2)
------------------ --------------
OS rate (24 months)(ii,iii) 22.2% 14.4%
------------------ --------------
PFS (secondary endpoint)
------------------ --------------
Number (%) of patients
with event 234 (87.3%) 236 (87.7%)
------------------ --------------
Hazard ratio (95% 0.80 (0.66, 0.96)
CI)
------------------ --------------
Median in months 5.1 5.4
(95% CI) (4.7, 6.2) (4.8, 6.2)
------------------ --------------
PFS rate (6 months) 45.4% 45.8%
------------------ --------------
PFS rate (12 months) 17.9% 5.3%
------------------ --------------
PFS rate (24 months)(iii) 11.0% 2.9%
------------------ --------------
ORR (secondary endpoint)(iv,v)
------------------ --------------
Number (%) of patients
with response 182 (67.9%) 156 (58.0%)
------------------ --------------
Odds ratio (95% 1.53 (1.08, 2.18)
CI)
------------------ --------------
DoR at 24 months(iii,iv) 13.5% 3.9%
------------------ --------------
Ongoing Imfinzi,
n (%)(iii) 32 (12%) 0
------------------ --------------
i. Etoposide plus investigator choice of carboplatin or
cisplatin chemotherapy.
ii. OS rate is an estimated proportion of patients alive at 24 months.
iii. Post-hoc analysis.
iv. Confirmed responses according to investigator assessment per RECIST v1.1.
v. Unconfirmed ORR was a prespecified secondary endpoint per protocol.
The safety and tolerability for Imfinzi plus chemotherapy was
consistent with the known safety profile of these medicines.
Results showed 62.3% of patients experienced a Grade 3 or 4 adverse
event with Imfinzi plus chemotherapy (all causes) versus 62.8% with
chemotherapy alone. The percentage of patients discontinuing
treatment (all causes) was 10.2% for Imfinzi plus chemotherapy and
9.4% for chemotherapy alone.
Imfinzi in combination with etoposide and either carboplatin or
cisplatin is currently under regulatory review for the treatment of
ES-SCLC in the 1st-line setting in the EU and Japan.
Updated results from the CASPIAN trial were presented during the
2020 American Society of Clinical Oncology ASCO20 Virtual
Scientific Program on 29 to 31 May 2020. Several presentations
featured during the meeting will showcase AstraZeneca's leadership
in lung cancer across early and late-stage disease and reinforce
the Company's biomarker-driven approach.
Small cell lung cancer
Lung cancer is the leading cause of cancer death among both 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 only 6% of all SCLC
patients 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 etoposide
and either carboplatin or cisplatin chemotherapy, or Imfinzi and
chemotherapy with the addition of a second immunotherapy,
tremelimumab, versus chemotherapy alone. In the 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, in Europe, South America, Asia and the Middle
East. The primary endpoint was OS in each of the two experimental
arms.
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.
Imfinzi is approved in the curative-intent setting of
unresectable, Stage III NSCLC after chemoradiation therapy in the
US, Japan, China, across the EU and in many other countries, based
on the Phase III PACIFIC trial. Imfinzi is approved for the
1st-line treatment of ES-SCLC in combination with chemotherapy in
the US and Singapore. Imfinzi is also approved for previously
treated patients with advanced bladder cancer in the US and a small
number of other countries.
As part of a broad development programme, Imfinzi is also being
tested as a monotherapy and in combination with tremelimumab, an
anti-CTLA4 monoclonal antibody and potential new medicine, as a
treatment for patients with NSCLC, SCLC, bladder cancer, head and
neck cancer, liver cancer, biliary tract cancer, cervical cancer
and other solid tumours.
Tremelimumab
Tremelimumab is a human monoclonal antibody and potential new
medicine that targets the activity of cytotoxic
T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the
activity of CTLA-4, contributing to T-cell activation, priming the
immune response to cancer and fostering cancer cell death.
Tremelimumab is being tested in a clinical trial programme in
combination with Imfinzi in NSCLC, SCLC, bladder cancer, head and
neck cancer and liver cancer.
AstraZeneca in lung cancer
AstraZeneca has a comprehensive portfolio of approved and
potential new medicines in late-stage development for the treatment
of different forms of lung cancer spanning different histologies,
several stages of disease, lines of therapy and modes of action. We
aim to address the unmet needs of patients with EGFR-mutated
tumours as a genetic driver of disease, which occur in 10-15% of
NSCLC patients in the US and EU and 30-40% of NSCLC patients in
Asia, with the approved medicines Iressa (gefitinib) and Tagrisso
and its ongoing Phase III trials LAURA, and FLAURA2.(6-8) We are
also committed to addressing tumour mechanisms of resistance
through the ongoing Phase II trials SAVANNAH and ORCHARD which test
Tagrisso in combination with savolitinib, a selective inhibitor of
c-MET receptor tyrosine kinase, along with other potential new
medicines. Enhertu a HER2-directed antibody drug conjugate is in
development for metastatic non-squamous HER2-overexpressing or
HER2-mutated NSCLC including trials in combination with other
anticancer treatments.
An extensive Immuno-Oncology development programme focuses on
lung cancer patients without a targetable genetic mutation which
represents up to three-quarters of all patients with lung
cancer.(9) Imfinzi, an anti-PDL1 antibody, is in development for
patients with advanced disease (Phase III trials POSEIDON and
PEARL) and for patients in earlier stages of disease including
potentially-curative settings (Phase III trials MERMAID-1, AEGEAN,
ADJUVANT BR.31, PACIFIC-2, PACIFIC-4, PACIFIC-5, and ADRIATIC) both
as monotherapy and in combination with tremelimumab and/or
chemotherapy. Imfinzi is also in development in the Phase II trials
NeoCOAST, COAST and HUDSON in combination with potential new
medicines from the early-stage pipeline including Enhertu.
AstraZeneca's approach to Immuno-Oncology
Immuno-oncology (IO) is a therapeutic approach designed to
stimulate the body's immune system to attack tumours. The Company's
IO portfolio is anchored by 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 monotherapy and in combination with
tremelimumab in multiple tumour types, stages of disease, and lines
of therapy, 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 has a deep-rooted heritage in oncology and offers a
quickly growing portfolio of new medicines that has the potential
to transform patients' lives and the Company's future. With six new
medicines launched between 2014 and 2020, and a broad pipeline of
small molecules and biologics in development, the Company is
committed to advance oncology as a key growth driver for
AstraZeneca focused on lung, ovarian, breast and blood cancers. In
addition to AstraZeneca's main capabilities, the Company is
actively pursuing innovative partnerships and investment that
accelerate the delivery of our strategy, as illustrated by the
investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates - and by championing the development
of personalised combinations, AstraZeneca has the vision to
redefine cancer treatment and, one day, eliminate cancer as a cause
of death.
AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development and commercialisation of prescription medicines,
primarily for the treatment of diseases in three therapy areas -
Oncology, 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 and
follow the Company on Twitter @ AstraZeneca .
Contacts
For details on how to contact the Investor Relations Team,
please click here. For Media contacts, click here.
References
1. World Health Organization. International Agency for Research
on Cancer. Available at
http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf.
Accessed May 2020.
2. LUNGevity Foundation. Types of Lung Cancer. Available at
https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed May 2020.
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 May 2020.
4. Kalemkerian GP, et al. Treatment Options for Relapsed
Small-Cell Lung Cancer: What Progress Have We Made? Journal of
Oncology Practice, 2018:14;369-370.
5. Cancer.Net. Lung Cancer - Small Cell. Available at
https://www.cancer.net/cancer-types/33776/view-all. Accessed May
2020.
6. Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on
Cytological and Histological Samples in Non-Small Cell Lung Cancer:
a Polish, Single Institution Study and Systematic Review of
European Incidence. Int J Clin Exp Pathol. 2013:6;2800-12.
7. Keedy VL, et al. American Society of Clinical Oncology
Provisional Clinical Opinion: Epidermal Growth Factor Receptor
(EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell
Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor
Therapy. J Clin Oncol. 2011:29;2121-27.
8. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a
Review of Available Methods and Their Use for Analysis of Tumour
Tissue and Cytology Samples. J Clin Pathol. 2013:66;79-89.
9. Pakkala, S, et al. Personalized therapy for lung cancer:
striking a moving target. JCI Insight. 2018;3(15):e120858.
Adrian Kemp
Company Secretary
AstraZeneca PLC
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