Breaking news from the American Society of Clinical Oncology (ASCO) meeting in Chicago is good news for patients with advanced or metastatic melanoma. Most patients who have metastatic melanoma standardly receive chemotherapy that can be quite toxic. Now there is a new weapon that’s been proven to improve survival for patients whose melanoma is characterized by the BRAF v600 mutation (which can be found by testing a tumor biopsy specimen that is surgically removed from each patient). Its name is trametinib.
The METRIC clinical trial tested standard chemotherapy (dacarbazine or paclitaxel) versus a new medication called trametininb for over 300 patients with advanced or metastatic melanoma. Trametinib is called a MEK inhibitor because it blocks the MEK protein along the molecular MAPK pathway which many melanoma cells use to grow. The lead author of the trial, Dr. Caroline Robert from the Insitut Gustave Roussy in Paris discusses the trial results here: http://www.onclive.com/conference-coverage/asco-2012/Dr-Robert-on-the-Trametinib-METRIC-Trial-Results. At 6 months, 81% of patients who received trametinib were alive versus 67% of patients who received chemotherapy. An absolute (not relative) overall survival improvement of nearly 15% for a new cancer treatment over the current standard is dramatic for patients with advanced disease. These results are even more compelling in that patients were allowed to “cross over” in their treatment from trametinib to chemotherapy if their disease worsened.
Another potential blockage point along the MAPK pathway of BRAF positive melanoma cell growth is inhibition of the BRAF protein itself. The drug dabrafenib has been shown effective in that regard. In fact, another recent clinical trial revealed a benefit for patients with advanced melanoma using a “one-two punch.” Blocking both BRAF with dabrafenib and MEK with trametinib appeared promising. The combination resulted in fewer side effects than treatment with a BRAF inhibitor alone, though with an increased incidence of fever: http://www.medpagetoday.com/HematologyOncology/SkinCancer/32747.
Tramatenib is just one example among nearly hundreds of so-called “targeted therapies” developed over the past decade. Most of these medicines cost millions to develop and manufacturers pass these costs on to consumers. If we wish to be responsible regarding health care costs, it’s crucial for us to evaluate these targeted therapies thoroughly with rigorous clinical trials. The METRIC trial appears to be a good example: well designed and implemented with the critical endpoint of a true overall survival benefit for patients.
- Patrick Maguire MD