By Stacy Kess
November 20, 2013
Ray Thomas takes two pink pills a day, one in the morning and one at night.
The tablets look unassuming, but are how the Liberty High School assistant football coach and former math and computer science teacher treats his lung cancer. It’s a medication called crizotinib, one of several targeted approaches based on genetic testing for specific mutations.
“I had no idea this existed,” Thomas said. “I’m in there expecting to be hooked up to chemo in a week and a half and (the doctor said), ‘No, we’re not doing that.’”
Thomas never smoked before he was diagnosed with lung cancer in spring 2013, though he had already faced two unrelated cancers prior to learning he had lung cancer. In fact, he wasn’t even aware there was a problem with his lungs.
“It was strange,” he said. He was on a trip to Morgantown, W.Va., walking the hilly terrain without problem, when the “got a call that, ‘Hey, we need to make an appointment for you with someone to see what’s wrong with your lungs.’ And I’m going, I didn’t know there’s anything wrong with my lungs.”
After his lung was drained and biopsied, he was told that he had a specific type of mutation that could be matched with a targeted oral chemotherapy, in this case crizotinib.
Such targeted therapy meant Thomas could maintain his active lifestyle – he walks about two miles a day in addition to coaching – and wouldn’t need to start intravenous chemotherapy immediately, though he was told he may need to have the traditional treatment at some point.
The real excitement is in how doctors are getting to those targeted therapies, according to oncologists.
Looking for mutations
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital is one of a handful of centers around the country using gene sequencing as a standard of care for stage-4 lung cancer patients.
“I personally find this very exciting,” said Dr. David Carbone, an oncologist and director of the OSUCCC - James Thoracic Oncology Program. “I would call it revolutionary. And this is kind of analysis is slowly working itself into clinical practice.”
Otterson said the current testing is a direct result of the human genome sequencing that began in the 1990s.
“The technology arose from that, and affects what we’re doing today,” he said.
In fact, what they are doing today is testing 50 genes extracted from a single sample of a tumor by biopsy for specific genetic mutations. The technology is called next-generation “multiplex” gene sequencing, and can assess for more than 2,500 mutations in a single reaction.
“Not only are we looking at several mutations at once, but we’re catching mutations we would not have caught before,” Carbone said. “It’s much more comprehensive a loot at mutation patterns than anywhere else in the country.”
Dr. Greg Otterson, co-director of the OSUCCC Thoracic Oncology Program, said in 2004, it became evident that different mutations responded to different drugs. He said once in a while a patient “at death’s door” would have a significant improvement when a specific chemotherapy agent was used. In 2009, the doctors began looking specifically for two genes: EGRF and KRAS. In 2010, doctors began looking for a third gene, ALK.
But until recently, each gene was tested separately for mutations. Now, with a single sample, the testing is down for the mutations in genes in about 10 days.
When the results come back, the mutations can be matched to the right drug.
“Targeted therapies: as an oncologist, we’ve been using them for decades,” Otterson said. “It’s just he sophistication of the testing that’s gotten a step up.”
Not a cure, but a better treatment
“Basically, lung cancer is a really terrible disease and has a very poor survival rate and not a very effective treatment,” Carbone said. “Twenty-five years ago, when I started, we had very little to offer patients.”
Now, there are approved targeted oral chemotherapy agents for both EGRF and ALK.
“Once you’ve got metastatic disease, for the vast majority of patients, I can’t tell them I’m going to cure them,” Otterson said. But he can tell them that they may be able to avoid the traditional chemo therapies longer.
Otterson said the oral agents are changing both the course of treatments and the outcomes for patients.
“Not only do patients get a better quality of life, but they get a better response to treatment,” he said. “What I expect is about a third of patients will have their tumor shrink from (IV chemotherapy), a third will have no change and a third will progress.”
But that’s not so with the targeted therapies. Response rates for erlotinib, an oral chemotherapy agent that targets a genetic mutation called EGFR, can be as high as 75 or 80 percent, Otterson said. And there’s fewer side effects.
For Thomas, the side effects have been so minimal – some swelling in one of his ankles and the occasional nausea – he wasn’t even sure if the symptoms were actual from the drug. This is not what he expected when he was told he had lung cancer; he imagined being hooked up to chemotherapy in the hospital, losing weight, being sick to his stomach and losing his hair.
The next gen testing allowed doctors to identify his tumor as driven by ALK, which is treatable by crizotinib. And as of right now, he said his doctors have called his disease course “dramatic improvement.”
“We’ve just started this next-gen panel, and we’re talking about what the next next-gen panel is going to be,” Otterson said. “To some extent, lung cancer in a lot of ways is leading the way.”
Carbone said he is excited at the progress that’s been made but “I think we shouldn’t get too satisfied with our level of progress because only about 30 percent of our patients have actionable mutations.”
That means the vast majority of patients still need standard chemotherapy treatments.
“We have a lot of room for improvement and we’re just learning to combine these treatments with other forms of treatment,” he said. “Still, lung cancer today has one of the worst five year survival rates as compared with other cancers.”