Any Cancer Can Be a 'Rare Cancer'

In the earliest days of science, researchers thought that if you had cancer, you just had cancer. Then, as classifications evolved, they thought if you

Stephen Gately

had lung cancer, you just had lung cancer. But now, advanced molecular profiling has necessitated a more complex analysis: You not only have lung cancer, you have EGFR mutated, KRAS mutated, or ALK gene rearrangement non-small cell lung cancer.

Welcome to the driving force behind the precision medicine movement. We’ve taken a general disease, narrowed that down to a specific disease classified by its organ of origin, and further classified the cancer by one or more defining genomic defects.

The process has turned the term “rare cancers” on its head. You might not consider lung cancer, which is diagnosed in 234,030 patients a year, a rare cancer. But what about ALK+ nonsmall cell lung cancer, which is diagnosed in just under 10,000 patients every year?

Because those 10,000 patients have a specific type of lung cancer, they don’t respond to the standard treatments that work for most people. Instead, they need drugs made specifically for their genomically defined cancer.

The same thing goes for those who have other cancers few people have heard of, like small intestine cancer, which also affects about 10,000 people a year. Small intestine cancer is a “rare cancer,” but so are certain types of more commonly diagnosed cancers-because cancer “rareness” means more than cancer incidence. It’s about the molecular makeup of each tumor.

That’s why the future of research for any cancer is entirely, and unequivocally, molecular. Drugmakers have caught on-and it has changed the calculus for cancer research.

Investigators should no longer pack as many patients as possible into a global clinical trial just to find responses to a new medicine in a few patients. Instead, they need to identify patients whose cancers share molecular defects, and match those molecular defects with a medicine that targets that particular defect.

You might think that finding very specific people with very specific diseases slows down research. And in a way, it can…at the start.

But here’s the reality: Targeted clinical trials yield the most dramatic results. When tumors rely on a single genetic mutation, medicines that target those mutations see response rates as high as 100%.

And if you’re a drugmaker, clinical investigator, or patient, once a new medicine makes headlines touting its benefit in nine of 10 patients, any slowdown is quickly reversed. People get excited and there is a singular focus on getting the medicine approved quickly by the FDA.

Then, it’s not about finding the right patients-the right patients find the right medicines.

That’s what happened with Gleevec, the milestone drug that marked the first step in molecular

profiling. Built for patients with chronic myeloid leukemia (a rare subset that affects about 10% of leukemia patients), Gleevec saw an 88% response immediately. These were the patients for whom other drugs had failed.

In many of these cases, you don’t need a lot of patients to respond in order to get a drug approved. They’re rare cancers, after all. This kind of drug discovery means that researchers can spend less time in development, get their drugs approved faster, and start helping patients immediately. It just requires a sound clinical strategy that targets the right people.

When I think of the impact that one small change could make on the lives of patients, it gives me hope. I think of patients with uveal melanoma, which has zero drugs approved for treatment. I think of patients with fibrolamellar hepatocellular carcinoma that impacts young adults and has no drugs approved for treatment.

Each is a rare cancer in its own right. Each has known molecular or genetic defects. We need to

find the right drugs to match to these cancers. Precision medicine provides physicians with the opportunity to avoid less effective treatments and focus on rationally selected medicines that improve clinical outcomes for patients. 

Stephen Gately, PhD, is President and CEO of TD2