New medicine listed on the PBS for the treatment of metastatic melanoma in Australia

The listing of Tafinlar^® (dabrafenib mesilate) on the Pharmaceutical Benefits Scheme (PBS) will lead to improved access to the medicine for melanoma patients in Australia from December 1st.

Tafinlar® (dabrafenib), treats unresectable stage III melanoma (melanoma that cannot be removed by surgery) or stage IV metastatic melanoma (melanoma which has spread to other parts of the body) in patients with BRAF V600 mutation.¹
Among those with melanoma, approximately half have a BRAF mutation, which is an abnormal change in a gene that can enable some melanoma tumours to grow and spread.^1-3

The approval and reimbursement of Tafinlar^® in Australia is based on positive results derived from several multi-centre global trials, including a Phase III study that showed significant improvement in progression free survival.^1,4-6

Professor Rick Kefford, medical oncologist and clinical researcher at Melanoma Institute Australia said, “Access to this new class of drugs through the PBS is a step forward for Australian patients with metastatic melanoma. Australian Clinical Investigators played a vital role in the development of dabrafenib and discovered the activity of the drug in brain metastases which are a major area of previously unmet medical need in the treatment of this disease.”

Tilly Ryan, CEO Melanoma Patients Australia, welcomed the new options and improved access for Australians with melanoma.

“We welcome new listings on the PBS of treatments for metastatic melanoma. The treatment for advanced melanoma has been relatively unchanged for the past forty years and we are pleased that in more recent years we are seeing developments in the treatment of metastatic melanoma, thereby providing Australian melanoma patients with greater treatment options. Melanoma Patients Australia applauds the ongoing research into melanoma and we look forward to the continued support of the Australian Government in making medical advances accessible and affordable to all Australian melanoma patients in Australia through PBS Listing,” said Ms Ryan.

About Tafinlar^® (dabrafenib)

BRAF is a key component of the MAPK pathway, which regulates the normal growth and death of cells, including skin cells.⁷ In approximately 50% of melanomas, a mutated BRAF protein in the MAPK pathway disrupts normal cellular regulation and promotes increased cell production.^1-3 A diagnostic test is required to identify patients with unresectable stage III or metastatic melanoma who have the BRAF V600 mutation.1 Tafinlar® (dabrafenib) binds to the mutated BRAF protein, which may lead to an inhibition of oncogenic signalling, thereby inhibiting the proliferation of tumour cells.¹

About Metastatic Melanoma

Melanoma is the most serious type of skin cancer and causes 75 per cent of skin cancer-related deaths.^8-9 Australia has the highest incidence of melanoma in the world and melanoma is often referred to as Australia's national cancer.⁹ More than 12,500 new cases of melanoma are diagnosed in Australia every year and 1,500 Australians die from melanoma each year.⁹ Typically, less than 5 per cent of all newly incident melanoma patients present with metastatic disease.¹⁰

Please review Tafinlar^® Product information before prescribing. The product information and consumer medicine information can be accessed at www.gsk.com.au

PBS Information: For the treatment of BRAF V600 mutation
positive unresectable stage III or stage IV malignant melanoma.
Authority required. Refer to PBS schedule for full information.

Tafinlar^® (dabrafenib mesilate) Minimum Product Information

Indications: Tafinlar^® is indicated for the treatment of patients with BRAF V600 mutation positive unresectable Stage III or metastatic (Stage IV) melanoma. Contraindications: Hypersensitivity to dabrafenib mesilate or any excipients. Precautions: Patients should be routinely monitored for ophthalmologic reactions during therapy. Efficacy and safety not established in wild-type BRAF melanoma. Pyrexia Interrupt therapy if temperature is ≥38.5°C. Monitor for signs/symptoms of infection. Restart Tafinlar^® when fever resolves with prophylactic non-steroidal anti-inflammatory products or paracetamol. Restart at reduced dose if fever associated with severe signs/symptoms. Cutaneous squamous cell carcinoma (cuSCC) Perform skin examination prior to initiation, every month throughout treatment, for up to 6 months after cuSCC treatment and for 6 months after Tafinlar^® discontinuation. New primary melanoma Monitor for skin lesions as described for cuSCC. Non-cutaneous malignancy Monitor as clinically appropriate. Pancreatitis Promptly investigate unexplained abdominal pain and measure serum amylase and lipase. Closely monitor when re-starting Tafinlar^® after episode of pancreatitis. Hyperglycaemia Monitor serum glucose levels as clinically appropriate in patients with pre- existing diabetes of hyperglycaemia. Other precautions Renal failure, effects on fertility, pregnancy (category D), lactation, paediatric use, use in elderly, genotoxicity and carcinogenicity. Interactions: Strong inhibitors or inducers of CYP2C8 or CYP3A4 Consider alternative agents. Caution if strong inhibitors coadministered with Tafinlar. Avoid coadministration of Tafinlar^® with potent inducers. Proton pump inhibitors Use with caution when administered with Tafinlar®. Medicinal products affected by induction of CYP3A4, CYP2C9, CYP2B6, CYP2C8, CYP2C19, UGT and transporters Avoid concomitant use if monitoring for efficacy and dose adjustment not possible. Warfarin Exercise caution, consider additional INR monitoring. Statins and OATP1B1 or OATP1B3 substrates Caution when co- administered with
Tafinlar^®. Adverse Events: Very common Papilloma, decreased appetite, headache, cough, nausea, vomiting, diarrhoea, rash, hyperkeratosis, alopecia, palmar-plantar erythrodysaesthesia, arthralgia, myalgia, asthenia, chills, fatigue, pyrexia , back pain, constipation, pain in extremity, and nasopharyngitis. Common Acrochordon, cuSCC, SCC in situ, keratoacanthoma, seborrhoeic keratosis, basal cell carcinoma, hypophosphataemia, hyperglycaemia, constipation, actinic keratosis, skin lesion, dry skin, erythema, influenza-like illness, LVEF decrease, abdominal pain, anaemia and neutropenia. Dosage and Administration: Confirmation of BRAF V600 mutation with approved/validated test required. Recommended dose is 150mg (two 75mg capsules) twice daily (total daily dose 300mg) at least one hour before or at least two hours after a meal. Dosage modifications/interruptions Not recommended for cuSCC or new primary melanoma. Interrupt therapy if temperature is ≥38.5°C. Dose adjust according to product information. Dose adjustments below 50mg twice daily not recommended. Daily dose should not exceed 150mg twice daily. Min PI v1

For full product information, information on GSK products or to report an adverse event involving a GSK product, please contact GSK Medical Information on 1800 033 109. GlaxoSmithKline Australia Pty Ltd. ABN 47 100 162 481. Melbourne, VIC. AUS/MEK/0017/13 Date of approval: December 2013
Tafinlar® is a registered trademark of the GlaxoSmithKline Group of Companies.

GlaxoSmithKline is 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 more information please visit www.gsk.com.au

This press release has been issued by Palin Communications on behalf of GlaxoSmithKline

MEDIA CONTACTS:

Professor Kefford has served on advisory boards sponsored by GlaxoSmithKline for which compensation was received and has been involved in clinical trials sponsored by GlaxoSmithKline. In relation to this media announcement, no compensation was provided to Prof Kefford, and the opinions expressed are his own. Prof Kefford has been briefed by GlaxoSmithKline on the approved use of this product.

References:

1. Tafinlar®Approved Product Information
2. Davies H et al, Nature, 2002;417:949-54
3. Curtin JA et al, N Engl J Med, 2005;353:2135
4. Ascierto PA et al, J Clin Oncol, 2013;31:3205-11
5. Long GV et al, Lancet Oncol, 2012;13:1087-95
6. Hauschild A et al, Lancet, 2012;380:358-65
7. National Library of Medicine. “Genetics Home Reference” Available at http://ghr.nlm.nih.gov/gene/BRAF (accessed Aug 2013)
8. Jerant AF et al, Am Fam Physician, 2000:62:357-68
9. Australian Institute of Health and Welfare & Australasian Association of Cancer Registries 2012. Cancer in Australia: an overview, 2012. Cancer series no. 74. Cat. no. CAN 70. Canberra: AIHW.
10. National Cancer Institute SEER: Melanoma of the skin. Available at: http://seer.cancer.gov/csr/1975_2010/results_merged/sect_16_melanoma_skin.pdf [Accessed November 2013].