Update on Lapatinib
GlaxoSmithKline PLC
15 May 2005
Issued - Sunday 15 May 2005, Orlando, Florida and London, UK - LSE
GLAXOSMITHKLINE ISSUES UPDATE ON LAPATINIB:
NEW CLINICAL DATA AND REGULATORY FILING PLANS
News From The American Society of Clinical Oncology (ASCO)
• Lapatinib shows 35% response rate in women with advanced breast cancer in
initial trial of the drug as first-line treatment.
• Other trials in refractory, previously treated breast-cancer patients report
additional data.
• GlaxoSmithKline intends to submit regulatory file in late 2006 or early 2007.
Thirty-five percent of women (14 of 40) with locally advanced or metastatic
breast cancer have responded to lapatinib as first-line therapy, according to
interim results of a study reported today at the annual meeting of the American
Society of Clinical Oncology (ASCO)1. The data are the first to be reported on
the use of lapatinib as a first-line therapy.
Lapatinib is an oral therapy targeting intracellular components of a receptor
known as ErbB2 and a second receptor, ErbB1, which have been implicated in the
growth of various tumor types. The Phase II trial (EGF 20009) tests lapatinib as
first-line therapy for breast-cancer patients with tumors that express large
amounts of ErbB2. An already marketed therapy, Herceptin(R) (trastuzumab), also
works through its effect on ErbB2, but it is a monoclonal antibody administered
by intravenous infusion. None of the patients in this lapatinib trial have been
treated with Herceptin.
"In this trial, we are seeing the strongest demonstration yet of the activity of
lapatinib in solid tumors, and the first demonstration of such activity by an
oral therapy directed at ErbB2," said Paolo Paoletti, M.D., senior vice
president, Oncology Medicine Development Center, GlaxoSmithKline (GSK), the
developer of lapatinib. "These data further demonstrate the potential of
lapatinib in breast cancer, and will help guide the expansion of our Phase III
program to support regulatory filings."
The data presented at ASCO were derived from an interim analysis planned at the
start of the trial and have been confirmed through an independent review. In the
35 percent of patients who experienced a partial response, tumor size was
reduced by at least 30 percent. An additional 35 percent (an additional 14 of
the 40 patients) showed stable disease through 12 weeks of therapy. All patients
will continue to be followed for disease progression as part of the planned
efficacy assessment. The trial, sponsored by GSK, will enroll a total of 130
patients.
The most frequently reported adverse events in this trial have been mild to
moderate itching, rash, diarrhea, acne, and dry skin. No adverse events deemed
drug-related, including cardiotoxicity, have been serious enough to be
categorised as Grade 3 or 4 by standard toxicity criteria.
"The efficacy and safety data from this trial point to the potential importance
of lapatinib as a treatment option for breast cancer patients," said George
Sledge, Jr., M.D., Ballve-Lantero professor of oncology and co-director of the
Breast Cancer Program, Indiana University Cancer Center.
Trials in previously treated, drug-refractory patients also are being presented
at ASCO. One is a Phase I study (EGF 10023) that has evaluated lapatinib in
combination with Herceptin, to evaluate whether two ErbB2-targeted therapies
acting at different sites of the receptor may enhance efficacy.2 At the San
Antonio Breast Cancer Conference last December, it was reported that 6 of 26
patients (23 percent) whose cancer progressed during Herceptin treatment later
experienced partial or complete responses when lapatinib was added to their
standard Herceptin regimen. Additional data from the now larger patient
population in this study will be presented on Tuesday, May 17.
Another study, presented on May 14, identified biomarkers from tissue and serum
that may help in predicting drug response as part of a continuing effort to
precisely direct lapatinib therapy to the populations that will most benefit
from it.3 This study relied on data from two Phase II trials (EGF 20002 and EGF
20008) in patients with late-stage disease who were administered lapatinib after
multiple other treatment options, including Herceptin, had been exhausted. In
this context, preliminary, overall efficacy results also were noted: Among
patients overexpressing ErbB2, the response rate ranged from 4.3 percent to 7.7
percent, and the stable-disease rate at 16 weeks from 8.6 percent to 14.1
percent; in patients not overexpressing ErbB2, there were no responders, and the
stable-disease rate was 2.2 percent. The final efficacy and safety analysis from
these two Phase II studies will be available later this year.
In light of all the data presented at ASCO, together with an expanded clinical
programme now in progress, GSK intends to revise the regulatory-filing strategy
for lapatinib. Previously, the company had considered an initial file in late
2005 on the basis of the two Phase II studies (EGF 20002 and EGF 20008) in
patients with late-stage disease, as noted above. Given the results of these
studies and the promising new data on lapatinib efficacy in breast cancer, GSK
now plans to submit a New Drug Application for lapatinib with the U.S. Food and
Drug Administration in late 2006 or early 2007 on the basis of data from Phase
III trials in progress.
Lapatinib has been granted fast-track status by the FDA for the treatment of
refractory advanced or metastatic breast cancer who have documented ErbB2
overexpression and who have failed previous therapy, including Herceptin.
S M Bicknell
Company Secretary
15th May 2005
About Lapatinib
Lapatinib, a small molecule that can be administered orally, inhibits the
tyrosine kinase components of ErbB1 and ErbB2 receptors. Stimulation of ErbB1
and ErbB2 is associated with cell proliferation, and with multiple processes
involved in tumor progression, invasion, and metastasis. Overexpression of
these receptors has been reported in a variety of human tumors and is associated
with poor prognosis and reduced overall survival. GSK is using advanced
technologies including pharmacogenetics to better define patient populations
that may respond to lapatinib.
Lapatinib is an experimental drug that does not have regulatory approval in any
country for any use outside of clinical trials. It is being developed by GSK as
an orally administered therapy for breast cancer and other solid tumors.
About Lapatinib Trials
Information about ongoing clinical trials of lapatinib in breast cancer can be
obtained by visiting http://www.4BreastCancerTrials.com or calling 800-563-7137.
Information is also available at http://www.clinicaltrials.gov (keyword:
GW572016), a website maintained by the US government, or at a toll-free number
of the National Cancer Institute's Cancer Information Service, 800-4-CANCER.
About Metastatic Breast Cancer
The World Health Organization reports that just over one million cases of breast
cancer are diagnosed annually. Breast cancer is the most common malignancy in
women and one of the leading causes of cancer death.
Approximately 10 percent of newly diagnosed breast-cancer patients have locally
advanced and/or metastatic disease; 20 to 85 percent of patients (depending on
initial stage, tumor biology, and treatment strategy) diagnosed with early
breast cancer will develop recurrent and/or metastatic disease.4 The median
survival time for women treated for metastatic breast cancer is two years.5
About GlaxoSmithKline
GlaxoSmithKline -- one of the world's leading research-based pharmaceutical and
healthcare companies -- is committed to improving the quality of human life by
enabling people to do more, feel better, and live longer. For company
information, visit GlaxoSmithKline at http://www.gsk.com.
# # #
Notes to editors:
Lapatinib is also designated as GW572016.
Herceptin(R) is a registered trademark of Genentech, Inc.
References:
1 H.L. Gomez et al. A phase II, randomized trial using the small
molecule tyrosine kinase inhibitor lapatinib as a first-line treatment in
patients with FISH positive advanced or metastatic breast cancer.
2 A.M. Storniolo et al. A Phase I, open-label study of lapatinib
(GW572016) plus trastuzumab; a clinically active regimen.
3 K.L. Blackwell et al. Determining relevant biomarkers from tissue and
serum that may predict response to single agent lapatinib in trastuzumab
refractory metastatic breast cancer.
4 C. Bernard-Marty et al. Facts and Controversies in Treatment of
Metastatic Breast Cancer. The Oncologist. 2004:9:617-632.
5 ibid.
Cautionary statement regarding forward-looking statements
Under the safe harbor provisions of the US Private Securities Litigation Reform
Act of 1995, the company cautions investors that any forward-looking statements
or projections made by the company, including those made in this announcement,
are subject to risks and uncertainties that may cause actual results to differ
materially from those projected. Factors that may affect the Group's operations
are described under 'Risk Factors' in the Operating and Financial Review and
Prospects in the company's Annual Report on Form 20-F for 2004.
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