GSK Study Showed Targeted Therapy Combination Achieved 14 Month Overall Survival in Patients with Advanced Breast Cancer
LONDON and PHILADELPHIA, Dec. 11 /PRNewswire/ -- In a clinical
study, women with an aggressive form of breast cancer experienced a
median survival of 14 months when treated with an investigational
combination of TYKERB® (lapatinib) plus HERCEPTIN®
(trastuzumab). The results of the Phase III study in HER2-positive
metastatic breast cancer were presented during the 32nd Annual
CTRC-AACR San Antonio Breast Cancer Symposium, held in San Antonio,
Texas (Dec. 9 - 13).
The study included 296 women with a type of breast cancer known
as HER2-positive disease, characterized by an overexpression of the
HER2 protein in the cancer cells. Patients enrolled in the study
experienced recurrence of breast cancer despite a median of three
prior trastuzumab-based therapies. The data presented at the San
Antonio congress showed that patients overcame resistance to
trastuzumab with the introduction of the lapatinib-trastuzumab
combination.
"The clinical benefits brought forth by the lapatinib and
trastuzumab combination are quite compelling and lead me to believe
the agents may be acting together to form a sort of 'dual blockade'
to obstruct the HER2 pathway necessary for the tumor to thrive,"
said primary investigator, Kimberly Blackwell, M.D., Duke
University Medical Center.
Patients in the study were randomized to receive single agent
lapatinib (1500 mg/daily) or a combination of lapatinib (1000 mg
p.o. daily) plus trastuzumab (2 mg/kg). For those patients treated
with monotherapy lapatinib, cross-over to the combination was
allowed if the disease progressed after at least four weeks of
therapy. Final analysis showed clinical activity for lapatinib in
the control arm. Women treated with monotherapy lapatinib
experienced a median overall survival of 9.5 months compared with
14 months when treated with the combination (median HR: 0.74,
p=0.026).
"It's possible that, by lapatinib working inside the cell and
trastuzumab working outside the cell, the combination of agents is
able to provide a more complete anti-tumor attack," said Blackwell.
"To achieve a survival advantage of greater than one year for this
aggressive form of breast cancer is very encouraging."
Final safety analysis showed the incidence of adverse events
were similar among both treatment groups with the exception of the
incidence of grade 1 and 2 diarrhea, which was significantly higher
in the combination group (P = 0.03). The incidence of grade 3 or
higher AEs was similar among treatment groups (7%).The most common
adverse events (incidence greater than or equal to 10%) were
diarrhea, nausea, rash, fatigue and vomiting. Of the Grade 3/4
adverse events observed, cardiac events were reported in three
patients on the combination arm and in one patient on the
monotherapy arm. One patient in the combination arm experienced
cardiac failure and later died due to pulmonary thromboembolism
that was caused by disease progression and/or study
medication.
"Very few clinical studies have shown a survival benefit in
metastatic breast cancer," said Steven Stein, M.D., Vice President,
Medicine Development, GSK Oncology. "It's very encouraging to see
the results gained by combining these two agents."
TYKERB is currently indicated in combination with Xeloda®
(capecitabine) for the treatment of patients with advanced or
metastatic breast cancer whose tumors overexpress HER2 and who have
received prior therapy including an anthracycline, a taxane, and
Herceptin (trastuzumab). TYKERB alone or in combination with
HERCEPTIN is not approved in this setting.
GSK in Oncology
GSK Oncology is dedicated to producing innovations in cancer
that will make profound differences in the lives of patients.
Through GSK's revolutionary 'bench to bedside' approach, we are
transforming the way treatments are discovered and developed,
resulting in one of the most robust pipelines in the oncology
sector. Our worldwide research in oncology includes collaborations
with more than 160 cancer centers. GSK is closing in on cancer from
all sides with a new generation of patient focused cancer
treatments in prevention, supportive care, chemotherapy and
targeted therapies. For more information about GSK Oncology, visit
www.gskoncology.com.
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 www.gsk.com.
To access the latest GSK news, visit http://us.gsk.com/. BOXED WARNING and Additional Important Safety Information
Hepatotoxicity - TYKERB has been associated with hepatotoxicity.
Hepatotoxicity (ALT or AST >3 times the upper limit of normal
and total bilirubin >1.5 times the upper limit of normal) has
been observed in clinical trials (<1% of patients) and
postmarketing experience. The hepatotoxicity may be severe and
deaths have been reported. Causality of the deaths is uncertain.
The hepatotoxicity may occur days to several months after
initiation of treatment. Liver function tests should be monitored
before initiation of treatment, every 4 to 6 weeks during
treatment, and as clinically indicated. If changes in liver
function are severe, therapy with TYKERB should be discontinued and
patients should not be re-treated with TYKERB.
Decreased Left Ventricular Ejection Fraction - TYKERB has been
reported to decrease LVEF. Caution should be taken if TYKERB is to
be administered to patients with preexisting cardiac conditions,
including uncontrolled or symptomatic angina, arrhythmias, or
congestive heart failure. Confirm normal LVEF before starting
TYKERB, and continue evaluations during treatment.
Patients with Severe Hepatic Impairment - If TYKERB is to be
administered to patients with severe hepatic impairment, dose
reduction should be considered.
Diarrhea - Diarrhea, including severe diarrhea, has been
reported during treatment with TYKERB and was the most common
adverse reaction resulting in discontinuation of TYKERB therapy.
Proactive management of diarrhea with anti-diarrheal agents is
important, and severe cases of diarrhea may require administration
of oral or intravenous electrolytes and fluids, and interruption or
discontinuation of therapy with TYKERB.
Interstitial Lung Disease/Pneumonitis - TYKERB has been
associated with interstitial lung disease and pneumonitis. Patients
should be monitored for pulmonary symptoms indicative of
interstitial lung disease or pneumonitis and if symptoms are
greater than or equal to Grade 3 (NCI CTCAE), TYKERB should be
discontinued.
QT Prolongation - TYKERB prolongs the QT interval in some
patients. TYKERB should be administered with caution to patients
who have or may develop prolongation of QTc. Hypokalemia or
hypomagnesemia should be corrected prior to TYKERB administration.
Baseline and on-treatment electrocardiograms with QT measurement
should be considered.
Pregnancy: Pregnancy D - TYKERB can cause fetal harm when
administered to a pregnant woman. Women should be advised not to
become pregnant when taking TYKERB. If this drug is used during
pregnancy, or if the patient becomes pregnant while taking this
drug, the patient should be apprised of the potential hazard to the
fetus.
Adverse Reactions - The most common adverse reactions (>20%)
during therapy with TYKERB plus capecitabine compared to
capecitabine alone were diarrhea (65%, 40%), nausea (44%, 43%),
vomiting (26%, 21%), palmar-plantar erythrodysesthesia (53%, 51%),
rash (28%, 14%), and fatigue (46%, 47%).
The most common grade 3 and 4 adverse reaction (NCICTC v3) with
TYKERB plus capecitabine compared to capecitabine alone were
diarrhea (14%, 10%) and palmar-plantar erythrodysesthesia (12%,
14%).
Please see full prescribing information, including BOXED WARNING. Notes to Editors:
TYKERB® is a registered trademark of the GlaxoSmithKline
group of companies in the United States.
TYVERB® is a registered trademark of the GlaxoSmithKline
group of companies in Europe.
XELODA® is a registered trademark of Roche Laboratories Inc.
HERCEPTIN® is a registered trademark of Genentech, Inc.
Enquiries:
Onsite Media Enquiries (US Media) Ken Inchausti (267) 809 7552
Onsite Media Enquiries (ex-US Media) Gregory Clarke (610) 405 0053
UK Media Enquiries: Philip Thomson (020) 8047 5502
David Outhwaite (020) 8047 5502
Stephen Rea (020) 8047 5502
US Media Enquiries: Nancy Pekarek (919) 483 2839
Mary Anne Rhyne (919) 483 2839
Kevin Colgan (919) 483 2839
Sarah Alspach (919) 483 2839
European Analyst/Investor Enquiries: David Mawdsley (020) 8047 5564
Sally Ferguson (020) 8047 5543
Gary Davies (020) 8047 5503
US Analyst/Investor Enquiries: Tom Curry (215) 751 5419
Jen Hill Baxter (215) 751 7002
Cautionary statement regarding forward-looking statements
Under the safe harbor provisions of the U.S. Private Securities
Litigation Reform Act of 1995, GSK cautions investors that any
forward-looking statements or projections made by GSK, 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 GSK's operations are
described under 'Risk Factors' in the 'Business Review' in the
company's Annual Report on Form 20-F for 2008.
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Source: GlaxoSmithKline
CONTACT: Onsite Media Enquiries (US Media): Ken Inchausti,
+1-267-809-7552; Onsite Media Enquiries (ex-US Media): Gregory
Clarke,
+1-610-405-0053; UK Media Enquiries: Philip Thomson,
+020-8047-5502, David
Outhwaite, +020-8047-5502, or Stephen Rea, +020-8047-5502; US Media
Enquiries:
Nancy Pekarek, +1-919-483-2839, Mary Anne Rhyne, +1-919-483-2839,
Kevin
Colgan, +1-919-483-2839, or Sarah Alspach, +1-919-483-2839;
European
Analyst/Investor Enquiries: David Mawdsley, +020-8047-5564, Sally
Ferguson,
+020-8047-5543, or Gary Davies, +020-8047-5503; US Analyst/Investor
Enquiries:
Tom Curry, +1-215-751-5419 or Jen Hill Baxter, +1-215-751-7002, all
of
GlaxoSmithKline
Web Site: http://www.gsk.com/
http://www.gskoncology.com/
http://us.gsk.com/
Posted: December 2009
