New Hope For Patients With Melanoma - The Most Deadly Form Of Skin Cancer And The Most Rapidly Increasing Cancer In The UK

Main Category: Melanoma / Skin Cancer
Also Included In: Cancer / Oncology
Article Date: 03 Jun 2009 - 4:00 PDT

email to a friend   printer friendly   view / write opinions   rate article

Roche and Plexxikon announced interim results from a phase I study with PLX4032 (R7204) a new, highly selective and potentially promising oral treatment for patients with advanced melanoma whose cancer harbours the BRAF mutation (known as mutation-positive). Patients treated with PLX4032 lived for a median of six months without their disease getting worse and more than half experienced significant shrinkage of their tumours; this included patients where the cancer had spread to the liver, lung and bone.1 Historically, less than 5% of metastatic melanoma patients are still alive five years after diagnosis.2

PLX4032 works in a highly innovative way by selectively targeting and destroying tumour cells carrying the BRAF mutation. BRAF is an important mediator of cell growth and division, but when mutated is known to cause 60% of melanomas, the most deadly form of skin cancer, and approximately eight percent of all solid tumours.

This was a phase I study involving 16 patients with BRAF positive melanoma and over half saw the extent of their cancer reduce by at least 30%.1 This experimental treatment will now be prioritised for phase II and III studies.

'PLX4032 has shown both tumour shrinkage and delay in tumour progression in patients whose tumours harbour a BRAF mutation, as well as improved quality of life for symptomatic patients,' stated Keith T. Flaherty, M.D., assistant professor at the Abramson Cancer Center of the University of Pennsylvania and principal investigator for the PLX4032 phase I clinical trial.

'Seven years after BRAF mutations were first identified we have validation that this mutation is a cancer driver and therapeutic target. In addition to a new and important chapter in the story of targeted therapy development in cancer, we are especially excited for our melanoma patients for whom there are few treatment options.'

Following these initial positive findings, Roche and its partner Plexxikon will evaluate the activity of PLX4032 in larger trials to support a potential registration program beginning later this year. If successful, it is expected to launch with a tissue based companion diagnostic test, representing another step forward in personalising cancer treatment. The two companies in their strong partnership are co-developing PLX4032 for potential use in a number of cancers harbouring the BRAF mutation. They are also co-developing the diagnostic test to select mutation-positive patients for clinical trials, and ultimately, for treatment with PLX4032.

Malignant melanoma is the most serious form of skin cancer. In the UK, more than 10,400 people are diagnosed with malignant melanoma each year3 and it is the most common kind of cancer for women in their 20's.4 Worryingly, the number of people diagnosed in the UK has quadrupled since the 1970's - making it the most rapidly increasing cancer3. Melanoma is treatable if caught early but patients who develop metastatic disease are rarely cured with available treatments. Only a small proportion of people (<5%) live more than two years once systemic metastases become evident.5

About the study

Promising preliminary findings reported in BRAF mutation-positive melanoma patients include:1

- PLX4032 has been well tolerated at therapeutic doses
- Partial responses (of at least 30% tumour volume reduction) in nine mutation-positive melanoma patients
- Regression of metastatic lesions in every site to which melanoma commonly spreads, including to the liver, lung and bone
- Disease control lasting up to 14 months with continuous therapy, with many patients still receiving treatment
- Interim median progression-free survival of approximately six months

By contrast, no treatment response was observed in a small group of patients without the BRAF mutation, and progression-free survival was less than two months, consistent with historical data.

Drug-related adverse events, including rash and photosensitivity, have been classified as mild in grade. Serious adverse events, including diagnosis of cutaneous squamous cell carcinoma, were observed in some patients after chronic treatment; however the safety profile has been warranted favourable for this population and the trial authorised to proceed to the next stage of investigation.

The PLX4032 data not only represent an important step forward in understanding and treating malignant melanoma, but also represent a significant advance in the use of biomarkers and diagnostic tools and the potential benefits of tailoring cancer treatment to individual patients.

References:

1 Flaherty K. Phase 1 study of PLX4032: Proof of concept for V600E BRAF mutation as a therapeutic target in human cancer. Oral presentation. Presented at ASCO 2009

2 The Healthcare Center, Facts About Metastatic Melanoma

3 Cancer Research UK Press Release 25 May 2009 See here Last accessed May 2009

4 Cancer Research UK Press Release April 2009. See here Last accessed May 2009

5 Boyle P, et al. World Cancer Report. IARC Press, Lyon, 2008

Source
Roche