This story recaps a recent New England Journal of Medicine article that reports a combination of two immunotherapy drugs — ipilimumab (sold under the trade name Yervoy) and nivolumab (sold as Opdivo) — are more effective at treating advanced melanoma than Yervoy is by itself. It’s exciting and interesting news, but the story does little more than scratch the surface of this topic. It does not adequately address study design, cost or potential harms, and does not include any independent, third-party input.
According the CDC, skin cancers are the most common forms of cancer in the United States. While the vast majority of skin cancers are basal cell, and are treatable, melanoma is a far more deadly form of the disease. In 2011, more than 65,000 people in the U.S. were diagnosed with melanoma of the skin. That same year, the disease killed more than 9,000 in the U.S. In additon to the human toll, skin cancer costs have escalated far more than the treatment costs of other cancers. The estimated annual costs of skin cancer treatment in the United States exceeds $8 billion, according to the CDC. Given the potential seriousness of a melanoma diagnosis, we think that it is untenable not to include the potential costs of new treatments along with a balanced description of the risks and benefits.
The story doesn’t address cost at all, and it’s a glaring omission. Yervoy costs around $30,000 per injection — and the combined cost of treatment with the two drugs would likely cost a patient (or that patient’s insurance provider) more than a quarter of a million dollars.
Admittedly, the published study in NEJM provides a bewildering array of information about outcomes that would confuse many medical professionals. Nevertheless, simply recounting the information from a press release or from the study abstract does little to inform the average reader. The outcomes reported by the story were tumor shrinkage and disease progression. These are what are known as “surrogate endpoints” — i.e. proxies for more important outcomes that patients care about, such as survival. Surrogates can certainly be useful and important indicators of a treatment’s effectiveness, but they may also fail to accurately reflect an outcome that’s important to the patient. In our view, a story that ONLY reports surrogate endpoints MUST provide some cautionary language about the limitations of those surrogates. In this case, the study hasn’t been going on long enough to determine whether the treatment confers a survival advantage, and the story appropriately called attention to that fact. Some additional caution on the limits of surrogates would also have been useful.
The story notes, “The combination of the two drugs also led to far higher levels of side effects, such as colitis and inflammation of lung tissue, at 54 percent versus 24 percent for Yervoy alone. Patients were also more likely to stop taking the combination of drugs.” That is useful information but a bit incomplete. The numbers reflect the percentage of patients who suffered grade 3 and 4 side effects and not just colitis and lung inflammation. But the story missed the most significant potential harm of all: death. As the paper itself notes, out of fewer than 100 patients who received the drug combination, “Three deaths were related to the combination therapy according to investigator assessment.” That’s worth mentioning.
The story describes the research as a “midstage study,” but doesn’t offer much more information. In reality it was a phase 1 dose escalation study. A bit more information would have been helpful For example, that it was a double-blind study, or that it was placebo-controlled, or that two patients were given the combined-drug treatment for every one patient who received only Yervoy. The story could also have noted that a larger study is already underway to see if the results hold up in a more diverse group of patients.
No disease mongering here.
While the story says that both drugs are made by Bristol-Myers Squibb, it fails to note that the study itself was supported by Bristol-Myers Squibb. That’s a significant oversight. Also, while the story quotes two people, one of them is a co-author on the study and the other is the Bristol-Myers Squibb employee who was responsible for developing the relevant drugs. An independent perspective would have been very welcome.
The story focuses solely on immunotherapy, and does not address surgery, chemotherapy, radiation therapy or other treatment techniques at all. The story would have been stronger if it had touched on, at least briefly, a fundamental question for readers: how is immunotherapy potentially better than other treatment techniques? We also think that a word about prevention would have been helpful to the reader.
The story makes clear that both drugs are currently on the market. However, the story doesn’t make clear to readers that both drugs have been approved by the FDA for use in treating advanced melanoma. That said, it’s not a major oversight for most readers.
The story does explain that Yervoy “is the first immunotherapy to extend survival in patients with advanced melanoma,” and that Opdivo “belongs to a promising new class of drugs called PD-1 inhibitors.” But the story doesn’t tell readers whether this is the first study to use multiple immunotherapy drugs in combination to treat melanoma. If it is the first such study, that’s worth including. And it’s not the first such study, the story would benefit from explaining how the new study differs from previous ones.
The story adds some additional information not found in the Bristol-Myers Squibb release.