After her melanoma, Cheryl Stratos is mostly back to a normal life, running a business and driving her teenage son to weekend events, but there are reminders that it could all come back: The sores all over her body, the high fevers, the hair loss -- even the possibility of a suddenly shortened life. For Stratos, of Virginia, and others who have benefitted from a class of revolutionary anti-cancer drugs known as BRAF mutation inhibitors, another tool in the fight against relapse has just been sharpened: Drug maker GlaxoSmithKline received FDA approval Wednesday for a new cocktail that includes a BRAF-targeting component.
The London company, which purchased Rockville-based Human Genome Sciences last year for $3.6 billion, had been hoping for expedited approval from the Silver Spring-based agency of Mekinist (trametinib) and Tafinlar (dabrafenib), a drug combo designed to limit melanoma-causing mutations.
Melanoma is less common than other types of skin cancer, but it also tends to be more serious, according to the American Cancer Society, with 10-year survival rates of between 24 and 68 percent for stage III diagnosis. The FDA approval process for the drug pair, the timeline for which was expanded by the FDA in May to set a new September deadline, was pegged by Scientific American as one of the most-watched medical approval processes in 2013.
Mekinist is an MEK inhibitor, which works by blocking enzymes that spur malignant protein growth. Therapies based around MEK inhibitors are increasingly pushed for use with a similar class of existing drugs -- including the ones that saved Stratos' life -- known as BRAF inhibitors. In the the case of GSK, that means a likely pairing of Mekinist with Tafinlar, its BRAF drug.
Both types of inhibitors work by turning off genetic switches, according to Dr. Antoni Ribas, a BRAF specialist at the UCLA Medical Center who has overseen Stratos' treatments.
"10 years ago, it was discovered that a nucleotype change in DNA -- a single change in this position -- led to 50 percent of melanomas," Ribas told The Baltimore Sun. "That led a protein called B-Raf to be turned on ... in 50 percent of those cells, it was like the switch was on all the time, telling those cells to grow."
This nonstop growth of malignant cells could be prevented and even reversed by disabling the BRAF switch, says Ribas, who is currently working with GSK on the pairing of the drugs. Unfortunately, the respite is often only temporary.
"With time -- not in all cases, but in the majority -- the melanoma still finds a way to grow [without BRAF triggering]," he said. "That's called acquired resistance."
While Stratos says her chances are good, many patients like her face relapse as that acquired resistance allows cancers to survive. Even though she has been lucky, the BRAF drug that saved her life has side effects: Going out in the sun, for example, is now virtually impossible, since her skin burns so easily. And even as she says her recovery has been better than many, she acknowledges that she sees treatment increasingly becoming a "maintenance program" like that endured by diabetes patients, rather than what she calls a "scorched-earth policy."
That fight against acquired resistance and renewed cancer growth is where a BRAF/MEK inhibitor pairing comes in. An MEK inhibitor like Mekinist can often block the next switch on the signaling pathway, Ribas says. BRAF/MEK pairings also show promise in reversing some side-effects of existing drugs by preventing the drugs' collateral wreckage of healthy signaling mechanisms. In other words, by combining two drugs that block different types of flawed, unhealthy communication within a cell, a hybrid treatment may actually avoid damaging healthy communication.
The joint approval comes days before the annual meeting of the American Society of Clinical Oncology in Illinois. That group meets from Friday through Tuesday at Chicago's McCormick Place.
Correction: An earlier version of this article misidentified the drug in the reference to "Mekinist" in paragraph four. The Baltimore Sun regrets the error.