Last updated on April 20, 2014 at 8:28 EDT

Afatinib*, Boehringer Ingelheim’s investigational compound, demonstrates progression free survival of almost one year in patients with EGFR mutation positive, advanced non-small cell lung cancer in pivotal phase III trial

June 4, 2012

LUX-Lung 3 trial results highlighted at the official ASCO Press Conference: Afatinib*
lung cancer progression compared to standard chemotherapy

BURLINGTON, ON, June 4, 2012 /CNW/ – The LUX-Lung 3 Phase III results
showed that lung cancer patients taking the novel compound afatinib*,
an irreversible ErbB Family Blocker, as a first-line treatment, lived
for almost one year before their disease progressed (progression-free
survival (PFS) of 11.1 months) versus just over half a year (PFS of 6.9
months) for those on standard chemotherapy (pemetrexed / cisplatin)(1).

Importantly, patients taking afatinib* with EGFR mutations (del19 and
L858R, accounting for 90% of all EGFR mutations studied in the trial)
lived for well over a year without progression (PFS of 13.6 months)
versus just over half a year (PFS of 6.9 months) for those in the
comparator arm(2).( )

“Increasingly, we are now considering a more personalized approach to
managing lung cancer,”  says Dr. Natasha Leighl, medical oncologist at
the Princess Margaret Hospital and President of Lung Cancer Canada.
“We’ve found that patients with specific genetic mutations – like in
the EGFR gene – will respond better to certain therapies. With this in
mind, it’s important that all Canadians with non-small cell lung cancer
be tested for their mutation status at diagnosis, similar to the way
breast cancer patients are tested for their genetic mutation status at
diagnosis, so that patients and their oncologists can make informed
treatment decisions.”

Boehringer Ingelheim’s pivotal phase III trial LUX-Lung 3 is
investigating the company’s molecule afatinib*, and is the largest and
most robust pivotal phase III clinical trial to date in EGFR (ErbB1)
mutation positive advanced lung cancer patients. The primary endpoint
was progression-free survival (PFS).

Full data from the trial will be presented today in a late-breaking oral
presentation at the 48th Annual Meeting of the American Society of
Clinical Oncology (ASCO) in Chicago.

“Not only did LUX-Lung 3 meet its primary endpoint, but it also showed
that afatinib*, especially in patients with EGFR mutations, almost
doubled the progression free survival time compared to chemotherapy.”
commented Prof. James Chih-Hsin Yang, Director of the Cancer Research
Center, College of Medicine, National Taiwan University, Taipei, Taiwan
and principal investigator of the LUX-Lung 3 trial. “Based on this
proven efficacy in the largest and most robust registration trial,
coupled with its novel mode of action, afatinib* may become one of the
most valuable treatment options for this distinct patient population.”

The most common drug-related adverse events observed in the afatinib*
treatment arm were diarrhea (95%), rash (62%), and paronychia (57%). 
The most common drug-related adverse events observed in the
chemotherapy arm (pemetrexed /cisplatin) were nausea (66%), decreased
appetite (53%), and vomiting (42%).  There was a low discontinuation
rate associated with treatment-related adverse events in the trial (8%
discontinuation rate for afatinib; 12% for chemotherapy).  One percent
of patients in the afatinib* arm discontinued due to diarrhea(3).

“Survival rates for patients with non-small cell lung cancer are
dissapointingly low, which is why new treatments, like afatinib, that
effectively target specific genetic mutations, in this case in the EGFR
gene, are desperately needed,” adds Dr. Normand Blais, medical
oncologist and director of the thoracic oncology program at the Centre
Hospitalier Université de Montréal.

Afatinib* is different from currently available targeted therapies in
that it irreversibly blocks the ErbB Family of receptors, meaning
afatinib* blocks EGFR (ErbB1) as well as the other relevant members of
the ErbB Family, all of which can be involved in pathways that help
tumour cells grow, migrate and metastasize.

“Data from LUX-Lung 3 show that in patients with EGFR genetic mutations,
afatinib demonstrated a significant and clinically meaningful delay in
the progression of NSCLC, compared with combination pemetrexed and
cisplatin,” said Berthold Greifenberg, MD, Vice President, Clinical
Development and Medical Affairs, Oncology, Boehringer Ingelheim
Pharmaceuticals, Inc.  “These results add to the growing body of
evidence supporting EGFR testing as an opportunity to inform and
personalize the treatment of patients with EGFR mutation-positive
NSCLC.  This further underscores Boehringer Ingelheim’s commitment to
advancing the research and development of its compounds with the goal
of improving the lives of patients with cancer.”

Notes to Editors

About LUX-Lung 3 Trial
LUX-Lung 3 is a large, randomized, open-label, Phase III registration
study comparing afatinib* to two chemotherapy agents, pemetrexed and
cisplatin, as first-line treatment for patients with stage IIIb or IV
NSCLC harbouring an EGFR mutation.  The study included 345 patients
with EGFR mutation positive NSCLC globally.  LUX-Lung 3 is the largest
pivotal phase III trial to date in patients with EGFR mutation positive
advanced, metastatic NSCLC and the first study in this population to
use pemetrexed / cisplatin as a comparator(4).

About Lung Cancer in Canada
According to the Canadian Cancer Society, in 2012 an estimated 25,600
Canadians will be diagnosed with lung cancer(5), and 20,100 will die from it(6). In fact, more people are estimated to die from lung cancer in 2012
than from colorectal, breast and prostate cancer combined(7). As the leading cause of cancer death in both men and women in Canada(8), an average of 55 Canadians die from lung cancer every day(9).

Lung cancer is also grossly under researched and under-funded. It only
gets 7 per cent of cancer-specific research funding and 0.1 per cent of
cancer donations, despite the fact that it causes 27 per cent of
cancer-related deaths(10).

About Afatinib*
Afatinib* is an investigational oral, once-daily, irreversible ErbB
Family Blocker that specifically inhibits epidermal growth factor
receptor (EGFR or ErbB1), human epidermal receptor 2 (HER2 or ErbB2)
and ErbB4(2), which is known to play a critical role in the growth and spread of the
most pervasive cancers and cancers associated with high mortality
(lung, breast, and head & neck cancers). Afatinib* is currently also in
Phase III clinical development in breast cancer and head and neck
cancer.  Afatinib* is currently not authorized for sale by Health
Canada; its safety and efficacy has not been established.

About Boehringer Ingelheim in Oncology
Building on scientific expertise and excellence in the fields of
pulmonary and cardiovascular medicine, metabolic disease, neurology,
virology and immunology, Boehringer Ingelheim has embarked on a major
research programme to develop innovative cancer drugs. Working in close
collaboration with the international scientific community and a number
of the world’s leading cancer centres, Boehringer Ingelheim’s
commitment to oncology is underpinned by using advances in science to
develop a range of targeted therapies for various solid tumours and
haematological cancers

The current focus of research includes compounds in three areas:
angiogenesis inhibition, signal transduction inhibition and cell-cycle
kinase inhibition. BIBF 1120, an angiogenesis inhibitor is currently in
Phase III clinical development in NSCLC and ovarian cancer.  In the
area of cell-cycle kinase inhibition, Boehringer Ingelheim is
developing an inhibitor of polo-like kinase 1 (Plk1), a protein that is
involved in the processes of cell division. The compound is in Phase II
development for acute myeloid leukaemia.

Boehringer Ingelheim’s oncology pipeline is evolving and demonstrates
the company’s continued commitment to advance the disease area.

About Boehringer Ingelheim (Canada) Ltd.
The Boehringer Ingelheim group is one of the world’s 20 leading
pharmaceutical companies. Headquartered in Ingelheim, Germany, it
operates globally with 145 affiliates and more than 44,000 employees.

Since it was founded in 1885, the family-owned company has been
committed to researching, developing, manufacturing and marketing novel
products of high therapeutic value for human and veterinary medicine.
As a central element of its culture, Boehringer Ingelheim pledges to
act socially responsible. Involvement in social projects, caring for
employees and their families, and providing equal opportunities for all
employees form the foundation of the global operations. Mutual
cooperation and respect, as well as environmental protection and
sustainability are intrinsic factors in all of Boehringer Ingelheim’s

In 2011, Boehringer Ingelheim posted net sales of 13.2 billion euro
while spending almost 24% of net sales in its largest business segment
Prescription Medicines on research and development.

The Canadian headquarters of Boehringer Ingelheim was established in
1972 in Burlington, Ontario, Canada and the Research and Development
Centre is located in Laval, Québec, Canada. Boehringer Ingelheim
(Canada) Ltd. is home to more than 750 employees including 170
scientists across the country.

*Afatinib is an investigational compound.
Its safety and efficacy has not yet been fully established and it is
currently not authorized for sale in Canada.

For more information please visit www.boehringer-ingelheim.ca


(1) Abstract no: LBA7500, LUX-lung 3: A randomized, open-label, phase III
study of afatinib versus pemetrexed and cisplatin as first-line
treatment for patients with advanced adenocarcinoma of the lung
harboring EGFR-activating mutations. Oral Presentation at 48(th) Annual Meeting of the American Society of Clinical Oncology (ASCO)

(2) Ibid.

(3) Ibid.

(4) Ibid.

(5) Canadian Cancer Society’s Steering Committee: Canadian Cancer Statistics 2012. Toronto, ON: Canadian Cancer Society; 2012, Page 8.

(6) Canadian Cancer Society’s Steering Committee: Canadian Cancer Statistics 2012. Toronto, ON: Canadian Cancer Society; 2012, Page 9.

(7) Ibid.

(8) Canadian Cancer Society’s Steering Committee: Canadian Cancer Statistics 2012. Toronto, ON: Canadian Cancer Society; 2012, Page 7.

(9) Canadian Cancer Society’s Steering Committee: Canadian Cancer Statistics 2012. Toronto, ON: Canadian Cancer Society; 2012, Page 9.

(10) Charity Intelligence Canada: Cancer in Canada. April 2011. Page 39.

SOURCE Boehringer Ingelheim

Source: PR Newswire