Most chemotherapy drugs are approved by the U.S. Food and Drug Administration (FDA) without evidence that they benefit survival or quality of life.
By 2030, the number of new cancer cases in the United States is expected to skyrocket by 45%, from 1.6 million to 2.3 million every year. Are we really winning the war on cancer? Sadly, in general, no, despite the hundreds of new anticancer drugs that have been introduced.
As I discuss in my video How Effective Is Chemotherapy?, the war on cancer has been likened to the war on terror. No matter how many drone strikes you do, it’s nearly impossible to kill all the bad guys, and no matter how precise the bombing, one must always consider the collateral damage. Toxicity from cancer therapy can be debilitating—and not just health-wise. There is also “financial toxicity.”
Some patented anticancer drugs can cost nearly a thousand dollars a day. Even with health insurance, the average cost to patients with stage IV breast cancer, for example, can run about $190,000. It’s bad enough to have to fight for your life; you shouldn’t have to face bankrupting your family at the same time. Sadly, it remains a common problem today.
Who can forget the apocryphal story of Walter White in “Breaking Bad,” who worked two jobs with health insurance and still couldn’t afford his cancer care? Now, not everyone is willing to start their own meth lab, but many are willing to go for broke. A large portion of cancer patients reported their willingness to declare bankruptcy or sell their homes to pay for treatment. Aren’t the high prices of cancer medicines justified if innovative, new treatments offer patients significant benefits? You may be shocked to find out that “many FDA-approved cancer drugs might lack clinical benefit.”
Well, then how did they become FDA-approved? “Most approvals of cancer drugs are based on flimsy or untested surrogate endpoints, and postmarketing studies rarely validate the efficacy and safety of these drugs on patient-centred endpoints.” Let me explain what that means. New chemotherapy drugs are increasingly approved based only on surrogate endpoints, which means instead of looking at what we really care about—survival or quality of life—drugs are being approved based on things like “response rate” or tumor shrinkage. But who cares if the tumor shrinks if it doesn’t actually extend your quantity or quality of life? It’s kind of counterintuitive, but just seeing a tumor shrink on a CT scan or an MRI is not necessarily correlated with improvements in symptoms or survival. In fact, most studies that have actually followed people over time found low correlations with survival. The most recent comprehensive analysis found 91% of studies of such validation trials found little correlation with overall survival.
Of 36 new chemo drugs approved by the FDA based on these kinds of surrogate endpoints, once they were actually put to the test in the real world, only one in seven was shown to extend life, half explicitly flopped, and the rest remain untested, revealing “that most cancer drug approvals have not been shown to, or do not, improve clinically relevant end points.” “Exorbitant drug prices are bad enough for treatments that work. Charging vulnerable patients for drugs without evidence that they actually improve patients’ survival and quality of life is unconscionable.”
Why doesn’t the FDA require proof that chemo drugs actually benefit patients before it approves them? Some drug companies say that requiring randomized, controlled trials with “meaningful measures” would take too long, but the study time reduction using surrogate endpoints rather than overall survival is estimated at just 11 months. So, instead of it taking 7.3 years to come to market, on average, it would take 8.2 years. Of course, we want to get these drugs out as soon as possible, but only if they’re actually going to help people.
Do cancer drugs improve survival or quality of life? “You don’t need to know, according to our broken regulatory system” in the United States—and things are not much better over in Europe. A systematic evaluation of chemo drug approvals showed that most entered the market without evidence they benefited survival or quality of life. Even years later, there was still no conclusive evidence that they offered any benefit, and, when they did, the gains were often marginal.
That’s why you see editorials in the Journal of the National Cancer Institute with titles like “Hans Christian Andersen and the Value of New Cancer Treatments,” alluding to Andersen’s tale The Emperor’s New Clothes. “These studies all converge on a singular conclusion: only a minority of new cancer drugs approved by US and European regulatory authorities in recent years deliver clinically meaningful benefits to patients…” In fact, some cancer-related deaths may be hastened, or even caused, by the toxic effects of chemotherapy rather than the cancer itself. Based on a review of tens of thousands of cancer patients, in as many as 27% of cases, the cancer treatment itself caused or hastened death. But it might be worth that risk if the potential benefit is large enough. That’s the subject of my next blog.
Doctor’s Note
What about preventing cancer in the first place? See Fighting the Ten Hallmarks of Cancer with Food and How Not to Die from Cancer.
Coming up? How Much Do New Chemotherapy Drugs Extend Life?.
