On Sunday, the Milwaukee Journal Sentinel and MedPage Today published the latest installment in their wonderful “Slippery Slope” investigative series on the dubious practice of approving new drugs based on “surrogate measures” rather than on actual health outcomes.
This latest article focuses on the cancer drug Afinitor (everolimus), which the U.S. Food and Drug Administration (FDA) has approved for the treatment of breast cancer, kidney cancer, a rare type of pancreatic cancer and two types of nonmalignant tumors.
As Journal Sentinel reporter John Fauber and MedPage Today reporter Coulter Jones point out, Afinitor has been shown to delay the growth, or progression, of tumors by a few months, but it has not been shown to help people live longer.
Write Fauber and Jones:
In 2012, the FDA approved Afinitor for a common type of advanced breast cancer known as hormone receptor-positive, HER2 negative. Of all the conditions [for which Afinitor has been approved], it has the biggest potential pool of patients. That type is found in up to 70% of breast cancers.
The FDA approval was based on a clinical trial using Afinitor in tandem with exemestane, another breast cancer drug, vs. a placebo and exemestane.
The trial, which involved women who had failed one of two other drugs, showed the Afinitor combination offered progression-free survival of eight months, compared with three months in those who got the placebo and the other drug alone.
But it was not shown to extend survival.
Serious side effects
Nor have clinical trials found any evidence that Afinitor improves patients’ quality of life. In fact, the drug produces some serious and debilitating side effects, including mouth sores, infections, fatigue, diarrhea, abdominal pain, fever, cough, headache and decreased appetite.
Write Fauber and Jones:
In the [clinical] trial for advanced breast cancer, 63% of those taking Afinitor had to cut the dose of the drug or temporarily stop treatment, compared with 14% who got a placebo. Some 24% had to stop using it altogether, compared with 5% who got a placebo.
And nearly one in five developed a potentially fatal lung condition known as noninfectious pneumonitis. …
Since 2009, the year the drug first got on the market, there have been nearly 9,000 reports of serious adverse reactions among Afinitor users, including more than 2,700 deaths and more than 3,100 hospitalizations.
A broader problem
Last year, Fauber and Jones reported that 74 percent of new cancer drugs approved by the FDA over the past decade had not been shown to actually extend or improve life, only to slow the growth of tumors.
A study published this past October in JAMA Internal Medicine made a similar finding. It reported that 67 percent of cancer drugs approved during a recent five-year period (2008-2012) received that approval based solely on surrogate measures of effectiveness.
“Our results suggest that the FDA may be approving many costly, toxic drugs that do not improve overall survival,” the authors of the study wrote.
And these are very expensive drugs. The price tag for Afinitor alone can be as high as $11,400 a month — a figure that has jumped $3,000 a month since 2014, Fauber and Jones report.
But the problem is much broader than cancer drugs. Previous Journal Sentinel/MedPage investigations have found that the FDA’s reliance on surrogate measures “has led to a steady stream of costly drugs of dubious value over the past decade — not just in cancer, but for conditions such as diabetes, low testosterone and obesity.”
Conflicts of interest
Fauber and Jones also point out that the studies the FDA relies on when approving new drugs often have a high potential for bias:
A Journal Sentinel/MedPage Today analysis found at least 10 published papers — all funded by Novartis [the maker of Afinitor] and written mostly by experts with financial ties to the company — that played up the benefits of the drug for breast cancer patients, such as touting progression-free survival.
Two-thirds of the 64 co-authors listed on the papers were doctors and other experts with financial conflicts of interest. This included individuals who were consultants, speakers, advisers or even employees of Novartis.
For instance, a 2013 paper funded by the company concluded that Afinitor did not negatively affect quality of life in breast cancer patients. Twelve of the 20 authors were consultants, speakers or employees of the company.
A year earlier, reviewers at the FDA came to a different conclusion, saying there was no proven quality of life benefit for the drug and noted there was a large portion of quality of life data missing from the clinical trial.
More to come?
Novartis told Fauber and Jones that it follows strict guidelines to ensure that its studies are bias-free. The company also pointed out to the reporters that Afinitor has been approved for use in more than 100 countries.
The company is also hoping that the FDA will soon approve Afinitor’s use for three more medical conditions.