# AstraZeneca Tagrisso demonstrates unprecedented disease-free survival

- Link: https://www.directorstalkinterviews.com/astrazeneca-tagrisso-demonstrates-unprecedented-disease-free-survival/412826013
- Published: 2020-05-29T07:13:11+01:00
- Author: Amilia Stone

Detailed results from the Phase III ADAURA trial showed **[AstraZeneca PLC](https://www.directorstalkinterviews.com/ftse-company/astrazeneca/azn.l)**(
[LON:AZN](https://www.directorstalkinterviews.com/ftse-company/astrazeneca/azn.l))
_Tagrisso_ demonstrated a statistically significant and clinically meaningful improvement
in disease-free survival in the adjuvant treatment of patients with early-stage (
IB, II and IIIA) epidermal growth factor receptor-mutated non-small cell lung cancer
after complete tumour resection with curative intent.

Results will be presented during the plenary session of the American Society of 
Clinical Oncology ASCO20 Virtual Scientific Program on 31 May (abstract #LBA5).

In the primary endpoint of DFS in patients with Stage II and IIIA disease, adjuvant
treatment (after surgery) with _Tagrisso_ reduced the risk of disease recurrence
or death by 83% (based on a hazard ratio [HR] of 0.17; 95% confidence interval [
CI] 0.12, 0.23; p<0.0001). DFS results in the overall trial population, Stage IB
through IIIA, a key secondary endpoint, demonstrated a reduction in the risk of 
disease recurrence or death of 79% (based on a HR of 0.21; 95% CI 0.16, 0.28; p<
0.0001).

At two years, 89% of patients in the trial treated with _Tagrisso_ remained alive
and disease free versus 53% on placebo. Consistent DFS results were seen across 
all subgroups, including patients who were treated with surgery followed by chemotherapy
and those who received surgery only, as well as in Asian and non-Asian patients.

> **Roy S. Herbst, MD, Ph.D., chief of Medical Oncology at Yale Cancer Center and
> Smilow Cancer Hospital, New Haven, CT and principal investigator in the Phase 
> III ADAURA trial, said: **“These data are transformative for patients with early-
> stage EGFR-mutated non-small cell lung cancer who face high rates of recurrence
> even after successful surgery and subsequent treatment with adjuvant chemotherapy.
> _Tagrisso_ will provide a much-needed new treatment option that has the potential
> to change the practice of medicine and improve outcomes for patients in this setting.”

> **José Baselga, Executive Vice President, Oncology R&D, said:** “The momentous
> results of the Phase III ADAURA trial for _Tagrisso_ demonstrate for the first
> time in a global trial that an EGFR inhibitor can change the course of early-stage
> EGFR-mutated lung cancer and provide hope for a cure. We are discussing these 
> outstanding data with regulatory authorities and look forward to bringing the 
> benefits of _Tagrisso_ to patients with early-stage disease.”

In April 2020, an Independent Data Monitoring Committee recommended for the Phase
III ADAURA trial to be unblinded two years early based on its determination of overwhelming
efficacy. At the time of data cut-off, overall survival (OS) data favoured _Tagrisso_,
but were not mature. The trial will continue to assess OS as a secondary endpoint.

The safety and tolerability of _Tagrisso_ in this trial was consistent with previous
trials in the metastatic setting. Adverse events at Grade 3 or higher from all causes
occurred in 10% of patients in the _Tagrisso_ arm versus 3% in the placebo arm as
assessed by the investigator.

_Tagrisso_ is approved for the 1st-line treatment of patients with locally advanced
or metastatic EGFRm NSCLC in the US, Japan, China, the EU and many other countries
around the world.

Several presentations featured during the ASCO20 Virtual Scientific Program will
showcase AstraZeneca’s leadership in lung cancer across early and late-stage disease
and reinforce the Company’s biomarker-driven approach.

**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) Lung cancer is broadly split into 
NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.^(2) A significant
portion of patients with resectable NSCLC eventually develop recurrence despite 
surgery (complete resection).^(3,4) Approximately 10-15% of NSCLC patients in the
US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.^(5-7) 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.^(
8) Approximately 25-30% of patients with NSCLC present with resectable disease at
diagnosis.^(9-11)

**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 with
complete tumour resection and adjuvant chemotherapy as indicated. In the experimental
arm, patients were treated with _Tagrisso_ 80mg once-daily oral tablets 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 is DFS in Stage II and IIIA patients and a key
secondary endpoint is DFS in Stage IB, II and IIIA patients. The data readout was
originally anticipated in 2022. The trial will continue to assess OS as a secondary
endpoint.

**Tagrisso**

_Tagrisso_ (osimertinib) is a third-generation, irreversible EGFR-TKI with clinical
activity against CNS 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. _Tagrisso_ is also being developed 
in the Stage III, unresectable setting (LAURA), in combination with chemotherapy(
FLAURA2) and in combination with potential new medicines to address resistance to
EGFR-TKIs (SAVANNAH, ORCHARD).

**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. AstraZeneca aims to address the unmet needs of patients with EGFRm 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.^(
5-7)

AstraZeneca is 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_ (trastuzumab deruxtecan), 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 late-stage Immuno-Oncology programme focuses on lung cancer patients
without a targetable genetic mutation which represents up to three-quarters of all
patients with lung cancer.^(12) _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_.

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