Here at the at annual meeting of the American Society of Clinical Oncology in Chicago, we are beginning to see the future of cancer therapy—and it raises a provocative question: will precision medicine become so precise, we risk turning off the much-needed investment of human, intellectual and financial capital that keeps progress flowing?
The sheer number of new drugs and new combinations of drugs being reported here at the world’s biggest, and most relevant cancer conference is staggering. Not all of them are ready for prime time, and some may never be successful in the clinic for large numbers of patients, but it is clear the era of old fashioned chemotherapy is diminishing and newer forms of therapies (targeted and immunotherapies among others) are on the rapid ascent.
But with progress, it’s becoming clear that a changing paradigm in cancer care that was predicted a number of years ago is now coming to life.
In the early 2000s, we started to see the evolution of what are called targeted therapies, which very simply stated are treatments that take advantage of changes in the cancer cell to interrupt their function, and lead to their death. As time went on, it became more clear that it would be possible to develop tests to help us figure out which patients would benefit from that treatment.
Such predictive tests—frequently called companion diagnostics—have not become available for all treatments, but for others, those tests have helped guide treatment. But in doing so, they have also narrowed the field of who can benefit from newly developed drugs. Perhaps some of the earliest and best known are tests that detect HER2—a marker for the drug trastuzumab (Herceptin), which was first used in breast cancer. In the HER2 example, about 25% of breast cancers have the marker, which means that same 25% of breast cancer patients might benefit from treatment with trastuzumab—but 75% will not. That 25% is a fairly large number of people.
Tests also became available for a mutation called EGFR in lung cancer patients. The number of lung cancer patients who have EGFR is less than HER2 in breast cancer, but still a relatively large number given (unfortunately) the large number of people diagnosed with lung cancer each year.
As we have progressed down this path, other markers became available, such as ALK in lung cancer. Now we started to get into the 5% range of patients who had the abnormality. For lung cancer, that may mean about 8,000-10, 000 people a year who would be eligible to receive drugs that target that abnormality.
As it turns out, those may have been the low hanging fruit of this approach. With our ability to further analyze the cancer genetic signature we are seeing smaller and smaller percentages of cancers with a marker that suggests which patients may benefit from a new drug under development. This week at the ASCO meeting, numbers as low as 1-3% are not uncommon .
So we continue to detect genetic abnormalities in cancer tissue, thanks to tests that sequence the cancer genome. And we use that knowledge to develop new drugs designed specifically to attack those vulnerabilities. But the further we go, the smaller the number of patients who might benefit. In the future, these markers may be found in less common cancers, making that 1% to 3% an ever smaller number. This is why we call it “personalized/precision medicine;” that’s the whole point.
So the question is: how are we going to be able to fund the development and clinical trials for these micro-treatments? If there aren’t many patients who may benefit from a particular therapy who is going to make the needed investments to make that happen?
A number of years ago—2006 in fact—a well-known cancer researcher and oncologist, Dr. Brian Druker, asked that very question in an editorial in the New England Journal of Medicine. There were two studies reported in that issue of the Journal about two new targeted therapies for patients with chronic myelogenous leukemia. At the time, a drug called imatinib (Gleevec) was being used to treat the disease successfully for many patients. These newer drugs described in research reports were effective in the treatment of patients whose disease progressed on imatinib. But the number of patients who would be eligible to receive the drug were few.
Dr. Druker asked the question how we could expect companies to invest in new drug development when the number of patients who may benefit from those drugs is so few? His answer was that we needed better, more focused and efficient clinical trials to encourage that investment, as well as more efficient means to advance the research and approval process for new drug development.
Ten years later we have the technologies and the opportunities to make our dreams a reality: our research has taken us quickly to a place where we can find many abnormalities in cancer cells, and companies are making the investments to develop new drugs. But “getting to go” for those drugs can be very expensive, and the number of patients who can receive the drugs is limited.
If you think the prices of new cancer therapies at $150,000 year today is a high price, buckle up your seatbelts because the costs could likely go higher.
This is not to minimize the remarkable value of targeted therapies. But if only 1, 2 or 3% of the patients have the target, will we be able to keep the costs of developing the drug sufficiently low so that we provide all who can benefit access to the medications at an affordable price?
Our clinical trials system hasn’t been particularly efficient, and dealing with that problem will have to be a topic for another day. You can see the dilemma: better science, more opportunities for new drugs, but the ability to get a return on that investment is limited. The result may be even higher costs than we are seeing today.
We all want better cancer treatments, we want more specific and less toxic cancer treatments, and we are moving down that path. But eventually we have to face the question: can we afford our success?
Time will tell, and the answers aren’t in. But we certainly should be asking the questions about what we can to do make this work better, along the lines of what Dr. Druker proposed. We cannot fail in our mission, simply because too many lives will depend on getting it right.