On the High Price of Cancer Drugs

Today's New York Times has a good story on the unevenness of cancer care around the country, and how insurers play a major role in what type of care cancer patients get. I recently received an email query from a journalist doing an article about cancer drugs and their rising pricetags. My response, reprinted here, sheds light on some of the issues not covered in the Times' front page story, but relevant to discussions about unevenness in care:

Cancer remains the great conundrum of modern medicine.

Despite more than a half century of intensive research and development by both the public and private sectors, we have yet to make major advances against most of the more than 100 forms of the disease. Average life expectancy (measured as cancer patients who survive for at least five years after diagnosis) has gone from about half of all patients three decades ago to about 60 percent today.

Scientists have made incredible strides against some forms of the disease: several forms of leukemia, testicular cancer, some forms of breast cancer. Screening has helped millions of people identify others early on -- cervical cancer and colon cancer, for instance -- which is when they are most treatable. But for many other solid tumor cancers -- of the lung, pancreas or liver, for instance -- detection is only the point at which one learns one has an incurable disease.

I once heard the traditional weapons used in cancer therapy described as knives, flamethrowers and poison. Or, to use the medical terminology, surgery, radiation and chemotherapy. Many patients get all three. And the success of those weapons is measured by extending the life expectancy of the person diagnosed with cancer. For a percentage of patients (how big depends on the form of cancer and how early it is detected), it can even be a cure. But for most, success is measured by postponing the inevitable. Cancer therapies are approved today that extend life by a few months. Few quarrel with that standard when new drugs come before the Food and Drug Administration. After all, one day it may be you having your life extended.

But when patients are told about these new drugs, the tradeoffs remain deeply troubling. Patients and doctors are very aware of the quality of life of people undergoing extensive chemotherapy after surgery and radiation. And when it is not successful in terms of a cure but has succeeded in slowing the cancer's progression, the end stage is still marked by extensive pain and physical deterioration. Pain management is a major issue in end-of-life cancer patient care. So, in practical terms, if a patient is told that taking Drug A after surgery and radiation may give you a chance of living 15-18 months instead of 4-12 months (hypothetical example), that person must weigh whether they want to put up with a year of multiple chemo treatments with their side effects (nausea, hair falling out, etc.) versus the extra time.

Most choose the extra time since there is always the hope that they be among the lucky ones for whom treatment succeeds. But for most, that hope is only that. In the majority of cancers not caught early in their development, mutant cells have broken away from the solid tumor and have landed somewhere else to relaunch the cancer in another organ.

The latest generation of cancer drugs -- targeted therapies -- is a product of the last quarter century's heavy public sector investment in biomolecular research, and holds out hope of changing the cancer treatment paradigm. After President Nixon launched the war on cancer in 1971, the U.S. began investing heavily in understanding cell interactions at the molecular level. From Harold Varmus' discovery of the first oncogene (the particular genes that go wrong when cancers strike) to the human genome project, we now have a much better understanding of how cells work and what goes wrong when cancer strikes. The result is that there are many targets on cells that new drugs can aim to inhibit.

Sometimes a new drug aimed at these targets works, and because they are targeted inhibitors, not cell killers, they are much less toxic than chemotherapy. But, sadly, it turns out that most of the new targeted therapies are no more effective than traditional chemo drugs. Fast-growing cancer cells are mutating all the time, and the laws of population genetics means those that survive in the new environment (the presence of the drug) will be those that are resistant to the drug. Over time, that becomes the dominant strain of the cancer. The result? Many of the new targeted therapies only slow the rate of cancer growth by a few months (Iressa, for lung cancer, was the classic case).

Another new class of targeted drugs are the anti-angiogenesis drugs like Avastin. These inhibit the formation of new blood vessels to feed the cancer. It's a great idea, first propounded by Judah Folkman. But cancers are fast-growing beasts and it appears to overwhelm the anti-angiogensis effect after a while. Avastin has proved to be much more effective at curbing macular degeneration (explosion of blood vessels in aging eyes) than in arresting cancer.

Now we finally get to the economics of all this, which are, to say the least, daunting given the prices the drug companies are setting on these new targeted therapies. Say before the arrival of a new targeted therapy you have a cancer where the median survival time is 24 months. That means you will probably live somewhere between six months and five years (hypothetical) after taking traditional chemo drugs in the wake of surgery and/or radiation. A few patients will even be cured, say 20 percent, the definition being that they survived five years.

Now a new targeted therapy comes along aimed at this cancer. It turns out that the drug raises the median survival time to 27 months even though the general shape of the bell curve and survival rate stay the same. In other words, more patients are living longer, but the underlying dynamics of the disease really hasn't changed. This is definitely FDA approvable. And the company, with FDA license in hand, decides this is worth $10,000 a month.

Let's do a cost-benefit analysis of this drug. If we look at all patients taking this drug as a group, we find that their life expectancy has been extended by three months on average. Given that the average person in the group will be taking the drug for over two years, that amounts to nearly a quarter million dollars in extra medical expenses per patient. That means patients' insurers are paying $1 million per additional year of life.

Most European health care systems balk at that level of expense. But in America, Medicare cannot use cost-effectiveness analysis to limit drug use. They are bound by a "reasonable and necessary" standard. If it extends life, that's reasonable and necessary, period.

Which approach is correct? I ask myself: what if it were me? Confronted with a likely death sentence, knowing everything that I know and have seen about cancer therapeutics, I have no idea how I would respond if my doctor told me tomorrow that I had a virulent form of the disease. Because I a fairly well informed consumer, my instinct is to say I would study the literature on all the potential approaches and reject those that seem like their benefits don't add enough to justify the pain (side effects) and cost.

That's easy to say when I'm in perfect health. But maybe I'd have a completely different attitude when given the hope that taking this expensive drug would potentially give me at least another three months (and maybe more) to visit with my grandkids.

Which brings me to my real bottom line when it comes to the new, targeted therapeutics for cancer. Isn't the real issue that $10,000 per month pricetag? Isn't what we really need is a better way to develop drugs so that they are affordable?

Posted by gooznews at July 28, 2007 06:38 PM