Promising results for dabrafenib in advanced melanoma

Jun 8 2012

By Helen Albert

The BRAF inhibitor dabrafenib shows promising results for treatment of advanced melanoma, both alone and in combination with the MEK inhibitor trametinib, show results from two studies presented at the American Society of Clinical Oncology Annual Meeting in Chicago, Illinois, USA.

The BREAK-3 study compared treatment with dabrafenib with that of standard dacarbazine chemotherapy for patients with previously untreated, advanced melanoma and mutations in the BRAF gene.

The researchers found that the risk for disease progression was reduced by a significant 70% in the dabrafenib group versus the dacarbazine group.

The rate of serious skin side effects was lower for dabrafenib than previously observed in patients treated with the the US Food and Drug Administration approved melanoma drug vemurafenib. Overall, 3% of patients on dabrafenib developed photosensitivity and 6% squamous cell carcinomas (SCCs) versus 12% and 12%, respectively, of patients treated with vemurafenib in a previous phase III study.

"For three decades, we had no new therapies for metastatic melanoma, but we're quickly gaining momentum. Last year, ipilimumab and vemurafenib were approved, and now dabrafenib could be on the horizon," explained principal investigator Axel Hauschild (University Hospital Kiel, Germany) who presented the research .

"These findings represent another advance for melanoma and form the foundation for further studies to evaluate the role of dabrafenib in combination with other drugs."

The second phase IB study investigated the potential of combining treatment with dabrafenib with that of trametinib, which inhibits MEK gene expression, for treatment of advanced melanoma.

In total, 77 patients who had no prior exposure to BRAF-targeted therapies, and therefore no resistance to these drugs, were treated with varying dose combinations of dabrafenib and trametinib.

The median progression-free survival time of these patients was 7.4 months, which is comparable to that seen in previous single agent studies of vemurafenib.

Similar to the BREAK-3 study, very few patients developed SCCs (2%) or actinic keratoses (2%) compared with in previous studies of vemurafenib. Other side effects were manageable and included fever, fatigue, and dehydration.

"It's fascinating to find such promising effects with this combination regimen. Not only are the two drugs causing shrinkage of the cancer, but we're seeing that a second anti-cancer therapy may actually suppress the side effects of the first," said Jeffrey Weber (H Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA) who presented the findings of the second study at the conference.

He explained that a phase III trial investigating the combined effects of dabrafenib and trametinib is currently ongoing.

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