Breast Cancer Treatment Tykerb
NEW BREAST CANCER TREATMENT APPROVED BY THE TGA
New therapy for women with ErbB2 (HER2)-positive metastatic breast cancer that has
progressed despite treatment with other therapies including Herceptin® (1)
GlaxoSmithKline Australia (GSK) today announced that its new breast cancer treatment TYKERB®
(lapatinib ditosylate) has been approved by the Therapeutic Goods Administration (TGA) and will
be commercially available in Australia for the first time.
Lapatinib is a treatment for patients with ErbB2 (HER2) positive advanced / metastatic breast
cancer, whose disease has progressed despite treatment with other therapies including Herceptin®
(trastuzumab).(2)
A submission for lapatinib to be listed on the Pharmaceutical Benefits Scheme (PBS) was recently
rejected.# GSK is considering the issues leading to the rejection in evaluating future steps.
Since the inception of the Medicare Herceptin Program, 59 per cent of patients with metastatic
ErbB2 (HER2) positive breast cancer have either withdrawn from treatment or died.(3) This
highlights the need for Australian women to access new TGA approved HER2 targeted therapies
that may help them to continue fighting their disease.
In recognising the importance of timely access to lapatinib, GSK will provide lapatinib free of
charge to eligible patients who are enrolled in the Tykerb Access Program (TAP) before 30
November 2007.
"It is essential that Australian women have access to this treatment which may help them to continue fighting their disease. GSK has made the decision to provide the treatment at no charge, as an interim measure, to ensure that Australian women are not subject to an additional financial burden at what is already a difficult time for them and their families." said Dr Michael Elliott, VP and Medical Director, GSK.
Lapatinib is a small molecule, once-daily targeted therapy that is taken in tablet form.(4) Lapatinib is
taken in combination with Xeloda® (capecitabine), a type of chemotherapy that is also taken in
tablet form. It is estimated that between 300-500 women a year would be suitable for the
treatment.
The most common side effects during therapy with the combination of lapatinib and Xeloda are
diarrhoea, nausea and vomiting, hand-foot syndrome, fatigue and rash(.6,7) These side effects are
generally manageable. People with heart, lung and liver problems should take the drug with
caution. Lapatinib may also interact with other drugs and patients should review with their doctor
the medicines they are currently taking to make sure they are not taking something that cannot be
taken with Tykerb.*
As a small molecule, lapatinib penetrates and works inside the tumour cells to target ErbB2
(HER2) receptors.(8)
Lapatinib was recommended by Australian Drug Evaluation Committee (ADEC) for approval by the
TGA on 1st June 2007. From 26th June 2007, lapatinib has been approved for use in Australia.
Medical Oncologist, Associate Professor Fran Boyle,University of Sydney, today commented on
the registration of lapatinib in Australia, saying: "The TGA’s approval of lapatinib in Australia is the
next step forward in treating and managing advanced ErbB2 (HER2) positive breast cancer in this
country."
"The registration of lapatinib is welcome news to Australian women with ErbB2 (HER2) positive
advanced / metastatic breast cancer. This particular group of women in Australia now have another
viable treatment option available."
Breast cancer is the most common invasive cancer diagnosed in females in Australia and is the
leading cause of death in females, accounting for about 2,600 deaths each year(.9,10) While breast
cancer can also be found in men, it is extremely rare.(11)
In 2006, the number of estimated new breast cancer cases was approximately 13,261.(12) This
number is expected to increase to 14,800 by 2011.(13) Of these, it is estimated that 25-30 per cent
will have ErbB2 (HER2) positive breast cancer.(14 )
About the submission for PBS listing
GSK’s submission for PBS listing of lapatinib has been rejected on the basis of ‘unacceptable
incremental cost effectiveness’.(15)
Lapatinib’s cost effectiveness was supported in GSK’s submission by a comparison to Herceptin.
However, as Herceptin is still not considered cost effective by the PBAC in the metastatic setting
and as such is not PBS listed for this use, the PBAC did not accept Herceptin as a cost-offset.
This makes it very difficult to demonstrate the cost effectiveness of lapatinib, which is indicated for
use in patients whose disease has progressed despite treatment with Herceptin, even in light of the
fact that lapatinib costs less than Herceptin.(16)
About the TYKERB Access Program (TAP)
With lapatinib now registered in Australia, GSK will provide lapatinib free of charge to eligible
patients who are enrolled in the TYKERB Access Program (TAP) before 30 November 2007.
To access the TAP patients must meet certain criteria, including the TGA approved indication for
lapatinib:
In combination with capecitabine for the treatment of patients with advanced or metastatic breast
cancer whose tumours overexpress HER2 (ErbB2) and whose tumours have progressed after
treatment with an anthracycline, a taxane and trastuzumab.
The TAP program will continue until 30 November 2007, when it will be reviewed for its continuing
viability. GSK will continue to fund the treatment for patients enrolled before 30 November until
their oncologist determines that there is no longer clinical benefit from the treatment.
Oncologists will be provided with notification of any proposed changes to the program.
About ErbB2 (HER2) positive breast cancer
ErbB2 (HER2) receptors play a key role in cell growth and survival.(17) People with ErbB2 (HER2)
positive metastatic breast cancer have a form of cancer which tends to be highly aggressive(18) and
is associated with a greater risk for disease progression and death if not recognised and
treated.(19,20)
Also known as advanced breast cancer, metastatic breast cancer is the term used to describe
cancer that has spread from the original site in the breast to other organs or tissues in the body.(21)
Continuing drug development aims to provide effective treatment options with limited toxicity.(22) The
main aim of treatment for metastatic breast cancer is to improve the patient’s quality of life by
reducing symptoms and to slow disease progression.(23)
About GlaxoSmithKline Oncology
GlaxoSmithKline is one of the world's leading research-based pharmaceutical and healthcare
companies committed to improving the quality of human life by enabling people to do more, feel
better and live longer.
*Patients should seek advice from their oncologist to discuss the suitability of lapatinib for them. A
copy of the Tykerb Consumer Medicine Information can be accessed online at
http://www.gsk.com.au/products_prescription-medicines_detail.aspx?view=407
PBS Information: This product is not listed on the PBS
MINIMUM PRODUCT INFORMATION. TYKERB: lapatinib ditosylate Indication: Tykerb, in combination with
capecitabine, is indicated for the treatment of patients with advanced/metastatic breast cancer whose tumours
overexpress HER2 (ErbB2) and whose tumours have progressed after treatment with an anthracycline, a taxane and
trastuzumab. Contraindications: No known contraindications. Precautions: Decreases in left ventricular ejection
fraction (LVEF); conditions that could impair left ventricular function; interstitial lung disease and pneumonitis; diarrhoea
including severe diarrhoea -proactive management with anti-diarrhoeal agents is important; concomitant treatment with
CYP3A4 inhibitors (e.g. ketoconazole, itraconazole or grapefruit juice) or inducers (e.g. rifampin, carbamazepine or
phenytoin ); moderate or severe hepatic impairment; pregnancy (category C); lactation. For more details, refer to full PI.
Interactions: Inhibitors or inducers of the CYP3A4 enzymes may alter Tykerb pharmacokinetics - co-administration
should proceed with caution, and clinical response and adverse events should be closely monitored. Tykerb inhibits
CYP3A4 and CYP2C8 in vitro at clinically relevant concentrations – caution should be exercised when dosing Tykerb
concurrently with medications that are substrates of these enzymes. Inhibitors or inducers of Pgp, BCRP and OATP1B1
may alter exposure and/or distribution of Tykerb. Tykerb may affect the pharmacokinetics of substrates of Pgp (e.g.
digoxin), BCRP (e.g. topotecan) and OATP1B1 (e.g. rosuvastatin). Bioavailability of Tykerb is affected by food. For
more details, refer to full PI. Adverse Events: Tykerb monotherapy: Very common: anorexia, diarrhoea, nausea,
vomiting, hyperbilirubinaemia, rash (including dermatitis acneform), fatigue. Common: decreased left ventricular ejection
fraction. Uncommon: interstitial lung disease/pneumonitis. Tykerb in combination with capecitabine, frequency
difference of >5% compared to capecitabine alone: Very common: dyspepsia, dry skin. Similar frequency to capecitabine
alone: Very common: stomatitis, constipation, abdominal pain, palmar-plantar erythrodysaesthesia, mucosal
inflammation, pain in extremity, back pain, insomnia. Common: headache. For more details, refer to full PI. Dosage and
Administration: Adults: 1250mg (five tablets) once daily continuously. Tykerb should be taken at least 1h before or at
least 1h after food. Tykerb is taken in combination with capecitabine. The recommended dose of capecitabine is
2000mg/m/day taken in 2 doses 12h apart on days 1-14 in a 21 day cycle. Capecitabine should be taken with food or
within 30min after food. A positive HER2 protein overexpression/gene amplification is necessary for selection of patients.
Treatment with Tykerb should continue until disease progression or unacceptable toxicity. Children: Efficacy and safety
has not been evaluated. Elderly: No overall differences in safety of Tykerb were observed between the elderly and
younger subjects. Cardiac events: Evaluate LVEF in all patients prior to treatment to ensure baseline LVEF within
institutional limits of normal. Evaluate LVEF at 8-12wk intervals. Discontinue Tykerb in patients with symptoms
associated with decreased LVEF Grade 3 (NCI CTCAE) or if LVEF drops below lower limit of normal. Restart at a
reduced dose (1000mg/day) after a minimum of 2wk if the LVEF recovers to normal and the patient is asymptomatic.
Pulmonary symptoms: Monitor patients for pulmonary symptoms. Discontinue Tykerb in patients with pulmonary
symptoms indicative of interstitial lung disease/pneumonitis Grade 3 NCI CTCAE. Other toxicities: Consider dose
adjustment if Grade 2 (NCI CTCAE) toxicity occurs for other adverse events. Restart Tykerb at 1250mg/d when the
toxicity improves to Grade 1. If the toxicity recurs, then Tykerb should be restarted at a lower dose (1000mg/d).
CYP3A4 enzymes: Dose adjustment is recommended during co-administration of Tykerb with inducers/inhibitors of
CYP3A4. PLEASE REVIEW PRODUCT INFORMATION BEFORE PRESCRIBING. Full Product Information is
available from the Medical Affairs and Pharmacovigilance Department at GlaxoSmithKline ph 1800 033 109.
®
GlaxoSmithKline Australia Pty Ltd. ABN 47 100 162 481. 1061 Mountain Highway, Boronia, VIC 3155. Tykerbis a
registered trade mark of the GlaxoSmithKline group of companies.
REFERENCES:
1
Geyer CE et al N Engl J Med 2006; 355: 2733-2743
2
Tykerb Approved Product Information, Issue 1
3
Australian Government Medicare Australia. Accessed on 14 August 2007
http://www.medicareaustralia.gov.au/providers/programs_services
4
Tykerb Approved Product Information, Issue 1
5
GSK submission to the Pharmaceutical Benefits Advisory Committee
6
Geyer CE et al N Engl J Med 2006; 355: 2733-2743
7
Tykerb Approved Product Information, Issue 1
8
Montemurro F et al Expert Opin Biol Ther 2007; 7: 257-268
9
Australian Institute of Health and Welfare & National Breast Cancer Centre 2006. Breast cancer in Australia: an overview, 2006.
Cancer series no. 34. cat. no. CAN 29. Canberra: AIHW
10
National Health and Medical Research Centre (NHMRC) & National Breast Cancer Centre. Clinical Practice Guidelines: Management
of advanced breast cancer. Canberra: Commonwealth of Australia, 2001
11
Australian Institute of Health and Welfare & National Breast Cancer Centre 2006. Breast cancer in Australia: an overview, 2006.
Cancer series no. 34. cat. no. CAN 29. Canberra: AIHW
12
Australian Institute of Health and Welfare & National Breast Cancer Centre 2006. Breast cancer in Australia: an overview, 2006.
Cancer series no. 34. cat. no. CAN 29. Canberra: AIHW
13
Australian Institute of Health and Welfare & National Breast Cancer Centre 2006. Breast cancer in Australia: an overview, 2006.
Cancer series no. 34. cat. no. CAN 29. Canberra: AIHW
14
Meric F et al J Am Coll Surg 2002;194: 488-501
15
Australian Government. Department of Health and Ageing. PBAC Outcomes by Meeting. Accessed on 20 August 2007.
http://www.health.gov.au/internet/wcms/publishing.nsf/Content/pbac-outcomes-by-meeting
16
GSK submission to the Pharmaceutical Benefits Advisory Committee
17
Hynes NE, Lane HA Nat Review Cancer 2005; 5: 341-54
18
Meric F et al. J Am Coll Surg. 2002;194(4):488-501
19
Carney WP et al Clin Chem 2003; 49(10): 1579-1598
20
Slamon DJ et al Science 1987; 235(4785): 177-182
21
National Breast Cancer Centre. Clinical Practice Guidelines: Management of advanced breast cancer. Canberra: Commonwealth of
Australia, 2001
22
Cristofanilli M Semin Oncol 2006; 33 (3 Suppl 9): S9-S14
23
Kataja VV et al. Ann Oncol 2005; 16 (Suppl 1):i10-i12
