May 21, 2012

New Drug for Advanced Melanoma: Potential Breakthrough

(Ivanhoe Newswire) — Some say the number of cases is growing at an epidemic rate! In fact, melanoma is the fastest growing cancer in the U.S. Now, a new study shows the drug, dabrafenib, has been shown to have the most activity of any systematic treatment to date against secondary melanoma tumours in the brain.

A phase 1 trial shows the new drug causes substantial shrinking of metastatic tumours in patients. Dabrafenib blocks the activity of the cancer-causing mutated form of the BRAF gene, which is seen in about half of melanomas.

BRAF is a known oncogene, a gene that when mutated causes cancer. About 50% of patients with metastatic melanoma have a BRAF mutation in their tumour and it occurs in many other common cancer types including thyroid, colorectal, ovarian, and lung. The most common BRAF mutations are Val600Lys and Val600Glu.

A total of 184 patients with incurable solid tumours were enrolled into the study (156 of these patients with metastatic melanoma) and given escalating doses of dabrafenib. The initial phase of the study was designed to establish a safe dose.

In the second phase, 150 mg of the drug was given twice daily to three groups of patients with BRAF-mutant tumours: those with advanced melanoma, with untreated melanoma brain metastases, and with other BRAF-mutant solid tumours.

"Brain metastases in most (nine out of ten) patients given dabrafenib reduced in size, with four patients' metastases completely resolving", Dr. Gerald Falchook from the University of Texas MD Anderson Cancer Center in the USA, was quoted saying.

"Patients with melanoma and brain metastases typically survive for less than 5 months; yet in this study, all ten patients were alive at this stage and two patients had durable antitumour activity with survival beyond 12 months. One patient remains on treatment at 19 months" Dr. Falchook is the lead co-author of the study along with Dr. Georgina Long from the Melanoma Institute Australia and Westmead Hospital in Sydney, Australia, were quoted saying.

Dabrafenib also showed antitumour activity (partial responses and stable disease) in BRAF-mutant non-small-cell lung, colorectal, papillary thyroid, and ovarian cancers, and in gastrointestinal stromal. The most common higher level side effects observed included cutaneous squamous-cell carcinoma (a less serious form of skin cancer; 11%), fatigue (8%), and pyrexia (6%). The authors conclude: "The high response rate in melanoma brain metastases and the near-equivalent progression-free survival in patients with Val600Lys or Val600Glu BRAF-mutant melanoma justify the inclusion of such patients in further trials of potent BRAF inhibitors."

"(These findings) are impressive for two reasons: no previous systematic treatment has shown this degree of clinical activity against melanoma brain metastases, and dabrafenib was not predicted to cross the blood-brain barrier in substantial quantities“¦Overall, the prospects for use of BRAF-targeted treatment in new patient populations are encouraging," Geoffrey Gibney and Vernon Sondak from H Lee Moffit Cancer Center and Research Institute, Florida, were quoted saying.

SOURCE: Lancet, May 2012