The FDA made news by approving the use of an immunotherapy drug to treat tumors based on a genetic marker in the tumor, rather than the organ where the tumor originated. But this story about the new approval for pembrolizumab (brand name Keytruda) overlooks life threatening risks, overstates the meaning of trial results, inaccurately describes the patients who are covered by the FDA action and neglects the disappointing track record of drug approvals based on surrogate endpoints, rather than real measures of survival or quality of life. To its credit, the story does report the very high cost of the drug and appropriately highlights the novelty of a drug approval based on a biomarker.
The credibility of news reports about medical treatments depends on resistance to boosterism and clear explanations of the limits of what the evidence shows. Few readers of this story would discern that there is no evidence that any patients given pembrolizumab lived any longer or any better than those receiving standard therapies. That basic omission cheats readers.
Readers have to get deep into the story, but they are eventually told about “Keytruda’s $100,000-per-year price tag.”
In some cases, we might give a passing grade to a story that tells readers that one trial “found that in 17 of 30 advanced cancer patients, pembrolizumab stopped or reversed the progression of cancer, and 24 patients were still alive a year after starting the drug,” but this story should have alerted readers to the fundamental difference between these sorts of trial results and what people really care about: “Does the drug extend or improve the lives of patients?”
This point is particularly important because of mounting evidence that the slowing of cancer progression and other surrogate endpoints may not really answer the important questions about survival and quality of life. For example, one review of the 36 cancer drugs approved by the FDA from 2008 through 2012 based on surrogate endpoints revealed that only five later showed real survival benefits. A follow-up review looked at 55 cancer drugs approved based on surrogate endpoints. Reviewers found evidence of trials eventually showing improved survival for only 10 of the 55 drugs.
The story does not alert readers to the serious risks of immunotherapy for cancer. The drug label begins with this alert: “KEYTRUDA can cause your immune system to attack normal organs and tissues in many areas of your body and can affect the way they work. These problems can sometimes become serious or life-threatening and can lead to death.”
The story also quotes a researcher gushing about the potential benefits of pembrolizumab, but does not report that this same researcher recently reported the case of a patient who suffered a severe case of scleroderma while taking the drug.
Not covering the downsides of immunotherapy is something we see a lot–for tips on how to write more accurately about this, see: Too many stories ignore or under-report the harms of cancer immunotherapies. Here’s what the public needs to know.
The story fails to report that the clinical trials the FDA cited in its announcement were all single-arm and uncontrolled; that is, none directly compared the experimental treatment to other therapies. What’s more, the total number of patients in all five trials was only 149. As mentioned above, the use of surrogate endpoints, such as tumor progression, instead of survival or quality of life, means the drug has yet to demonstrate its ultimate worth.
The story reports that the new drug approval may apply to about 4 percent of advanced cancers, but it highlights a description of affected patients that is simply not accurate. The story states the FDA approved pembrolizumab “for treatment of solid tumors in any organ so long as the malignancy bears a specific genetic signature.” But what the FDA announcement states is that the approval is limited to “patients with solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options and patients with colorectal cancer that has progressed following treatment with certain chemotherapy drugs.”
In other words, patients who have already tried standard treatments without success.
There is a reference lower down in the story to “the treatment of patients with metastatic cancers that have failed all other treatments,” but there is no clear linkage to the important limitation in what the FDA approved.
The story does not tell readers anything about who paid for or managed the drug trials. It also does not report that one of the researchers quoted in the story, Dr. Bert Vogelstein, has received payments from pharmaceutical companies related to work on pembrolizumab, and that he also has a patent pending, as he stated in a New England Journal of Medicine disclosure statement.
The story strongly implies that pembrolizumab is better than existing cancer treatments for patients with the relevant genetic marker, but that is a claim that has yet to be tested, since none of the trials included any direct comparisons between the new drug and existing treatments.
The story reports that pembrolizumab is currently being sold under the brand name Keytruda.
A key element of the story, that this is the first FDA approval based on a biomarker, rather than the organ in the body where the tumor originated, is accurate and newsworthy.
The story appears to include original reporting.