# AstraZeneca’s Tagrisso approved in the US for early lung cancer

- Link: https://www.directorstalkinterviews.com/astrazenecas-tagrisso-approved-in-the-us-for-early-lung-cancer/412949798
- Published: 2020-12-21T07:18:51+00:00
- Author: Amilia Stone

**[AstraZeneca plc](https://www.directorstalkinterviews.com/ftse-company/astrazeneca/azn.l)**(
[LON:AZN](https://www.directorstalkinterviews.com/ftse-company/astrazeneca/azn.l))’
s _Tagrisso_ (osimertinib) has been approved in the US for the adjuvant treatment
of adult patients with early-stage epidermal growth factor receptor-mutated (EGFRm)
non-small cell lung cancer (NSCLC) after tumour resection with curative intent. 
_Tagrisso_ is indicated for EGFRm patients whose tumours have exon 19 deletions 
or exon 21 L858R mutations as detected by an approved test.

The approval was granted under the US Food and Drug Administration’s (FDA) Real-
Time Oncology Review (RTOR) pilot program. Five other countries participated in 
a concurrent submission and review process through FDA’s Project Orbis.

While up to 30% of all patients with NSCLC may be diagnosed early enough to have
potentially curative surgery, disease recurrence is still common in early-stage 
disease and nearly half of patients diagnosed in Stage IB, and over three quarters
of patients diagnosed in Stage IIIA, experience recurrence within five years.^(1-
4)

The approval was based on results from the ADAURA Phase III trial where _Tagrisso_
demonstrated a statistically significant and clinically meaningful improvement in
disease-free survival (DFS) in the primary analysis population of patients with 
Stage II and IIIA EGFRm NSCLC, and also in the overall trial population of patients
with Stage IB-IIIA disease, a key secondary endpoint.

> **Roy S. Herbst, MD, PhD, chief of Medical Oncology at Yale Cancer Center and 
> Smilow Cancer Hospital, New Haven, CT and principal investigator in the ADAURA
> Phase III trial, said:** “Adjuvant _Tagrisso_ has demonstrated an unprecedented
> disease-free survival benefit for early-stage lung cancer patients with EGFR mutations
> who face high rates of recurrence even after successful surgery and subsequent
> chemotherapy. This approval reinforces how critical it is to test all lung cancer
> patients for EGFR mutations before deciding how to treat them and regardless of
> their stage at diagnosis. This will help ensure as many patients as possible can
> benefit from this potentially practice-changing treatment.”

> **Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: **“
> For the first time, a targeted, biomarker-driven treatment option is available
> to patients in the US with early-stage EGFR-mutated lung cancer. This approval
> dispels the notion that treatment is over after surgery and chemotherapy, as the
> ADAURA results show that _Tagrisso_ can dramatically change the course of this
> disease. We remain committed to treating cancer patients earlier, when they may
> still have a chance of being cured.”

Adjuvant treatment with _Tagrisso_ reduced the risk of disease recurrence or death
by 83% in the primary endpoint of DFS in patients with Stage II and IIIA disease(
hazard ratio [HR] 0.17; 95% confidence interval [CI] 0.12-0.23; p<0.0001). DFS results
in the overall trial population of patients with Stage IB-IIIA disease showed _Tagrisso_
reduced the risk of disease recurrence or death by 80% (HR 0.20; 95% CI 0.15-0.27;
p<0.0001). At two years, 89% of patients treated with _Tagrisso_ remained alive 
and disease free versus 52% on placebo after surgery, the current standard of care.
The safety and tolerability of _Tagrisso _in this trial_ _was consistent with previous
trials in the metastatic setting.

_Tagrisso_ was recently granted Breakthrough Therapy Designation for patients in
the early-stage disease setting by the US FDA. In April 2020, an Independent Data
Monitoring Committee recommended for the ADAURA trial to be unblinded two years 
early based on a determination of overwhelming efficacy. Investigators and patients
continue to participate in the trial and remain blinded to treatment. The results
from the ADAURA trial were presented during the plenary session of the American 
Society of Clinical Oncology ASCO20 Virtual Scientific Program in May 2020 and were
recently published in The New England Journal of Medicine.

The US regulatory submission was reviewed under the FDA’s RTOR pilot program which
aims to ensure that safe and effective treatments are available to patients as early
as possible. Five national health authorities collaborated with the FDA on this 
review through Project Orbis, an initiative of the FDA Oncology Center of Excellence,
which provides a framework for concurrent submission and review of oncology medicines
among international partners. These included Health Canada, the Australian Therapeutic
Goods Administration, the Brazilian Health Regulatory Agency (Anvisa), Swissmedic,
and Singapore Health Sciences Authority. The UK Medicines and Healthcare products
Regulatory Agency participated in the review as an observer.

In China, _Tagrisso_ is under priority review for the adjuvant treatment of patients
with early-stage EGFRm NSCLC based on the ADAURA Phase III trial. This indication
is also under regulatory review in the EU and additional global submission discussions
are ongoing.  

_Tagrisso_ is a once-daily oral tablet approved for the 1st-line treatment of patients
with locally advanced or metastatic EGFRm NSCLC and for the treatment of locally
advanced or metastatic EGFR T790M mutation-positive NSCLC in the US, Japan, China,
the EU and many other countries around the world.

**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.^(5) Lung cancer is broadly split into 
NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.^(6) The majority
of all NSCLC patients are diagnosed with advanced disease while approximately 25-
30% present with resectable disease at diagnosis.^(1-3)

For patients with resectable tumours, the majority of patients eventually develop
recurrence despite complete tumour resection and adjuvant chemotherapy.^(4) Early-
stage lung cancer diagnoses are often only made when the cancer is found on imaging
for an unrelated condition.^(7-8)

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients
in Asia have EGFRm NSCLC.^(9-11) These patients are particularly sensitive to treatment
with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which block the cell-signalling
pathways that drive the growth of tumour cells.^(12)

**ADAURA**

ADAURA is a randomised, double-blinded, global, placebo-controlled Phase III trial
in the adjuvant treatment of 682 patients with Stage IB, II, IIIA EGFRm NSCLC following
complete tumour resection and adjuvant chemotherapy as indicated. Patients were 
treated with _Tagrisso_ 80mg once-daily oral tablets or placebo for three years 
or until disease recurrence.

The trial enrolled in more than 200 centres across more than 20 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. The
trial will continue to assess overall survival.

**Tagrisso**

_Tagrisso_ (osimertinib) is a third-generation, irreversible EGFR-TKI with clinical
activity against central nervous system metastases. _Tagrisso_ 40mg and 80mg once-
daily oral tablets have received approval in the US, Japan, China, the EU and many
countries around the world for 1st-line EGFRm advanced NSCLC and EGFR T790M mutation-
positive advanced NSCLC.

**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.

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