Earlier this year, the Food and Drug Administration approved a two-drug treatment for deadly cases of the skin cancer called melanoma. Tampa's Moffitt Cancer Center played a leading role in the discovery.
In a lab the size of a basketball court, Moffitt scientist Kieran Smalley and his team study human genes and proteins involved in different kinds of cancer. Their machines whir and clang, but the researchers don't seem to hear it.
Dr. Smalley has a particular interest in stage 4 melanoma – the kind that’s so advanced neither surgery nor drugs will help. Half of late-stage melanoma cases are triggered by a gene mutation, called B-Raf. There's a way to block it, Dr. Smalley says.
"In an extremely short 8 years, we actually had progressed from having a gene to having a drug”, said Smalley.
Dozens of patients at Moffitt, along with some other centers, tried the B-Raf inhibitor.
“Although the strategy appeared incredibly effective at first," Smalley said, "the patients only tended to respond to the therapy for approximately half a year."
Dr. Jeffrey Weber, director of the melanoma research center at Moffitt, says tumors that respond to B-Raf inhibitors eventually develop resistance.
They tried giving a second drug, called Mek. It blocks signals from a different place on the same molecular pathway.
Dr. Weber’s favorite analogy for the two-drug treatment is a thief speeding down a highway.
“Giving a B-Raf and Mek inhibitor is like blocking the road, laying the spikes down and blocking all the exits", Weber said. "The thief is invariably going to get caught."
Dr. Smalley said it worked better than anyone predicted.
“And the amazing part about it is the patients actually had fewer side-effects", said Smalley.
Moffitt had the largest group of patients in the clinical trial that combined the B-raf and Mek drugs. The combo therapy had a median survival of about two years, Dr. Weber said.
"You open the chart, to see the patient on this combination B-Raf/Mek trial here at week 48, week 60, here week 72, here week 96 and all of a sudden you realize all these patients are coming back two years later still in remission and you're thinking, 'Wow, that’s pretty impressive!'”, Weber said.
The two-drug therapy – called a doublet – works fast, as Dr. Weber discovered. He was sitting on his porch one Saturday afternoon when he got a call about a patient he had seen just the day before.
“My first thought was, 'Oh no, he’s got some horrendous side effect, he’s going to have to stop his treatment, he’s got some problem", described Weber. "So he got on the line; I asked him what was going on. He was very impressed by the fact that his routine pain medicines, which had been given for a number of weeks before starting treatment, he felt he didn’t to take them anymore.”
The patient, a realtor from southwest Florida, had been taking OxyContin. He needed it, with a bone lesion in his right leg and a tumor in his left thigh. But now, to Dr. Weber’s astonishment, the man was going for a walk.
“He said I just want to make sure there's no problem all of sudden not needing pain medicines," Weber recalled. "I said, 'Not at all, this is working unbelievably quickly to shrink your tumor.' So literally within 24 hours the guy obviously had evidence of regression, that’s why he wasn’t using his pain medicines. He went on to have a near-complete remission. We just saw him last week; he’s out three years. That’s the kind of thing that sticks in your mind. You think, 'Boy, this combination is pretty potent.'"
That leads to the inevitable question of whether science has arrived at the point where a stage 4 melanoma diagnosis may not be an automatic death sentence.
Weber says, "I think you’re thinking of the 'C word' for cure and it is entirely possible that either with this combination or immunologic treatment or both that we’ll be able to cure patients with melanoma, or at least render the disease a chronic disease.”
It’s similar to the way HIV infected patients are now living for years, even decades, by taking multiple drugs several times a day.
“So it seems as if we’re in a new era, where all patients are going be treated with doublets of drugs," Weber said.
"At Moffitt, where we’re engaged in cutting-edge care, we’re beyond that, we’re into triplets.”
FDA approved the two-drug therapy for melanoma in January. When Moffitt had a press conference to announce it, one of those who came was Dawn Dion, who had been in the clinical trial.
“When it was first diagnosed, I didn’t expect to survive," she said. "When you go on line -- don’t do it, folks, it isn’t pretty -- that’s what they tell you. You’re going to die.”
What really threw her was looking at her children.
“My youngest one was six. All I could think was, 'Who’s going to help her? Who’s going to raise her?'”
The answer, it turns out, is Mrs. Dion herself. She said she owes her life to Moffitt and the combination-drug trial.
“It’s really allowed me to be with my children and be a mom, and I couldn’t be more grateful for that.”
The brand names for the B-Raf and Mek inhibitors are Tafinlar and Mekinist; both are marketed by GlaxoSmithKline.