- Osimertinib will be made available via the Cancer Drugs Fund
(CDF) to patients in England with completely resected early-stage
IB-IIIA EGFR mutation-positive (EGFRm) non-small cell lung cancer
(NSCLC).1
- Currently, patients with this type of lung cancer are treated
with the intention of cure; however, many relapse because treatment
is limited to surgery and adjuvant chemotherapy.2
- Unprecedented data from the ADAURA clinical trial show that
osimertinib, the first approved targeted oral therapy in this
setting, can reduce the risk of disease recurrence or death
(disease-free survival) by 80% in patients with stage IB-IIIA EGFRm
NSCLC versus placebo.3
AstraZeneca today announced that Tagrisso (osimertinib) is now
available as an adjuvant treatment option after complete tumour
resection in adult patients in England with stage IB-IIIA non-small
cell lung cancer (NSCLC) whose tumours have epidermal growth factor
(EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations
via the Cancer Drugs Fund (CDF).1 Treatment with osimertinib is
subject to a three-year clinical stopping rule.1 This follows a
positive final recommendation from the National Institute for
Health and Care Excellence (NICE).
Professor Eric Lim, Professor of Thoracic Surgery at The
Royal Brompton Hospital, said: “This is a significant milestone
in the treatment of lung cancer in England as there remains an
urgent need for new personalised therapies even in early-stage
disease that have the potential to improve results of established
treatments such as surgery. Data show that osimertinib, a
well-tolerated treatment, reduces the risk of cancer recurrence or
death by 80% in patients with early-stage EGFR mutation-positive
non-small cell lung cancer after a successful operation. It is
vital we identify eligible patients with EGFR mutations early in
the treatment pathway to ensure they can access this treatment to
potentially improve and extend their lives.”
Lung cancer accounts for over one in five (21%) of all cancer
deaths in the UK,4 and more than 48,000 people in England are
diagnosed with NSCLC every year,5 with around 12% having tumours
with EGFR mutations.6 Patients with early-stage NSCLC often undergo
surgery with curative intent as standard of care – however, disease
recurrence within five years of surgery remains high, and has been
reported to occur in 45% of Stage IB, 62% of Stage II, and 76% of
Stage III patients.2
Jenny Abbott, co-chair of patient organisation EGFR Positive
UK, said: “Early diagnosis, coupled with early preventative
treatment, is key to improving long-term survival and we welcome
this decision, which means that patients diagnosed in England with
early-stage lung cancer will now continue to have access to this
important potential life-extending treatment.”
In the ADAURA Phase III trial, adjuvant treatment (after
surgery) with osimertinib in patients with stage II-IIIA EGFRm
NSCLC reduced the relative risk of disease recurrence or death
(disease-free survival) by 83% compared to placebo (HR = 0.17;
99.06% CI, 0.11 to 0.26; P<0.0011).3 Survival without disease
recurrence at two years was 90% (95% CI 84-93) for osimertinib and
44% (95% CI 37-51) for placebo.3 When looking at the broader group
of patients (stage IB-IIIA) – a secondary endpoint – the percentage
of patients who were alive and disease-free at 24 months was 89%
(95% CI, 85 to 92) in the osimertinib group and 52% (95% CI, 46 to
58) in the placebo group. The overall hazard ratio for disease
recurrence or death was 0.20 (99.12% CI, 0.14 to 0.30; P<0.001),
which equates to an 80% risk reduction.3
The announcement follows authorisation of a license extension by
the Medicines and Healthcare products Regulatory Agency (MHRA) in
May for osimertinib as monotherapy in this indication – the first
authorisation issued under Project Orbis; a global programme
designed to deliver faster patient access to innovative cancer
treatments.7 Simultaneously, an agreement was reached with NHS
England and NICE to enable early access to osimertinib for patients
in England. The NICE recommendation announced today means that
patients will continue to be eligible for treatment with
osimertinib via the Cancer Drugs Fund.1
Tom Keith-Roach, President, AstraZeneca UK, said: “The
Government’s Life Sciences Vision recognises how integral early
diagnosis and rapid access to innovative medicines are for
improving outcomes for people with cancer, and the chain of events
leading to today’s NICE recommendation is testament to this. From
the MHRA, to NICE and NHS England, we welcome the collaborative
engagement that has enabled us to bring the first precision
medicine for early-stage lung cancer to patients as quickly as
possible.”
Arun Krishna, Head of Oncology, AstraZeneca UK, said: “We
are delighted with this positive recommendation which builds on the
initial early access authorisation achieved through Project Orbis
and reaffirms the role that this potentially life-extending
treatment can have for some people with early-stage lung cancer.
It’s now critical that everyone with non-small cell lung cancer –
no matter what stage of disease – is tested for the presence of
EGFR mutations to determine whether osimertinib could be a
potential treatment option.”
Across the ADAURA, FLAURA and AURA studies for osimertinib, very
common adverse reactions included: diarrhoea (47% all grades; 1.4%
> grade 3), stomatitis (24% all
grades; 0.5% > grade 3), rash (45%
all grades; 0.7% > grade 3), dry
skin (32% all grades; 0.1% > grade
3), paronychia (33% all grades; 0.4% > grade 3), pruritus (17% all grades; 0.1%
> grade 3), platelet count
decreased (53% all grades; 1.2% >
grade 3), leucocytes decreased (65% all grades; 1.2% > grade 3), lymphocytes decreased (62% all
grades; 6.1% > grade 3) and
neutrophils decreased (33% all grades; 3.2% > grade 3).8 Common adverse reactions included:
epistaxis (5.3% all grades; 0 >
grade 3), interstitial lung disease (3.7% all grades; 1.1%
> grade 3), Palmar-plantar
erythrodysaesthesia syndrome (1.7% all grades; 0 > grade 3), alopecia (4.6% all grades; 0
> grade 3), urticaria (1.9% all
grades; 0.1% > grade 3) and blood
creatinine increased (9.4% all grades; 0 > grade 3).8
NOTES TO EDITORS
About osimertinib
Osimertinib monotherapy is licensed in the United Kingdom
for:
- the adjuvant treatment after complete tumour resection in adult
patients with stage IB-IIIA non-small cell lung cancer (NSCLC)
whose tumours have epidermal growth factor receptor (EGFR) exon 19
deletions or exon 21 (L858R) substitution mutations
- the first-line treatment of adult patients with locally
advanced or metastatic NSCLC with activating EGFR mutations
- and for the treatment of adult patients with locally advanced
or metastatic EGFR T790M mutation-positive NSCLC. 8
Osimertinib was discovered and developed in the UK by
AstraZeneca scientists. It is a third generation, orally
administered EGFR TKI, a targeted therapy for advanced EGFR
mutation-positive NSCLC.
In normal cells, EGFR plays a central role in regulating cell
division and death; however, mutations in the EGFR can cause
excessive cell growth and division. Osimertinib works by binding to
the mutated EGFR thereby blocking the cell signalling pathway that
drives the growth of tumour cells in NSCLC.9
For more information about osimertinib, a summary of product
characteristics (SMPC) can be found here:
https://www.medicines.org.uk/emc/product/1985/smpc.
ADAURA
The license for osimertinib in early-stage NSCLC is based on
data from ADAURA – a randomised, double-blind, global,
placebo-controlled Phase III trial in the adjuvant treatment of 682
patients with Stage IB, II and IIIA EGFR mutation-positive NSCLC
following complete tumour resection and adjuvant chemotherapy as
indicated. Patients were treated with osimertinib 80mg once-daily
oral tablets or placebo for three years or until disease
recurrence.
The trial enrolled patients in more than 185 centres across 24
countries, including the US, in Europe, South America, Asia and the
Middle East. The primary endpoint was DFS in Stage II and IIIA
patients and a key secondary endpoint was DFS in Stage IB, II and
IIIA patients.
The data readout was originally anticipated in 2022. In April
2020, an Independent Data Monitoring Committee recommended for the
trial to be unblinded two years early based on a determination of
overwhelming efficacy. Investigators and patients continue to
participate and remain blinded to treatment. The trial will
continue to assess overall survival.
About lung cancer
Lung cancer is the most common cause of cancer death in the UK,
accounting for one in five (21%) of all cancer deaths.4 NSCLC is
the most common type – more than 48,000 people in England are
diagnosed with NSCLC every year,5 with around 12% having tumours
with EGFR mutations.6 These patients are particularly sensitive to
treatment with EGFR-tyrosine kinase inhibitors (TKIs) which block
the cell-signalling pathways that drive the growth of tumour
cells.9 Approximately 25-30% of patients with NSCLC present with
resectable disease at diagnosis.10,11,12
The UK has one of the worst five-year survival rates for lung
cancer in Europe.13
AstraZeneca
AstraZeneca 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. AstraZeneca operates
in over 100 countries and its innovative medicines are used by
millions of patients worldwide.
AstraZeneca is based in five different locations across the UK,
with its global headquarters in Cambridge. In the UK, around 8,300
employees work in research and development, manufacturing, supply,
sales and marketing. We supply 40 different medicines to the
NHS.
For more information, please visit www.astrazeneca.co.uk and
follow us on Twitter @AstraZenecaUK.
References
- National Institute for Health and Care Excellence. Final
Appraisal Document. Osimertinib for adjuvant treatment of EGFR
mutation-positive non-small-cell lung cancer after complete tumour
resection. Issue date: 30 November 2021.
- Pignon JP, Tribodet H, Scagliotti GV, et al. Lung Adjuvant
Cisplatin Evaluation: a pooled analysis by the LACE Collaborative
Group. J Clin Oncol. 2008;26:3552-3559.
- Wu YL, Tsuboi M, He J, et al. Osimertinib in resected
EGFR-mutated non–small-cell lung cancer. N Engl J Med.
2020;383:1711-1723.
- Cancer Research UK. Lung cancer mortality statistics. Available
at:
http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer/mortality#heading-Zero.
Last accessed: November 2021.
- Cancer Research UK. Lung cancer statistics. Available at:
https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer#heading-Two.%20Accessed%20August%202021.
Last accessed: November 2021
- Midha A, Dearden S, McCormack R. EGFR mutation incidence in
non-small cell lung cancer of adenocarcinoma histology: a
systematic review and global map by ethnicity (mutMapII). Am J
Cancer Res. 2015;5;2892-2911.
- GOV.UK. Guidance on Project Orbis: what the Project Orbis
initiative is and MHRA involvement in this regulatory path.
Available at:
https://www.gov.uk/guidance/guidance-on-project-orbis. Last
accessed: November 2021.
- Tagrisso (osimertinib). Summary of Product Characteristics. 14
May 2021. Available at:
https://www.medicines.org.uk/emc/product/1985/smpc#gref. Last
accessed: November 2021.
- Cross DA, et al. AZD9291, an irreversible EGFR TKI, overcomes
T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer
Discov. 2014;4:1046-1061.
- Cagle PT, Allen TC, Olsen RJ. Lung cancer biomarkers: present
status and future developments. Arch Pathol Lab Med.
2013;137:1191–1198.
- Datta D, Lahiri B. Preoperative evaluation of patients
undergoing lung resection surgery. Chest. 2003;123:2096–2103.
- Le Chevalier T. Adjuvant chemotherapy for resectable
non-small-cell lung cancer: where is it going? Ann Oncol.
2010;21:196–198.
- Allemani C, et al. Global surveillance of trends in cancer
survival: analysis of individual records for 37,513,025 patients
diagnosed with one of 18 cancers during 2000–2014 from 322
population-based registries in 71 countries (CONCORD-3). Lancet.
2018 March 17; 391(10125): 1023–1075.
doi:10.1016/S0140-6736(17)33326-3.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20211129005759/en/
UK Media Enquiries Emma White, AstraZeneca: 07385 516437
/ emma.white1@astrazeneca.com Alex Larkinson, Edelman: 07980 687255
/ alex.larkinson@edelman.com