This story never adequately characterized the results of a randomized controlled trial called AZURE on the use of zoledronic acid (Zometa) for early stage breast cancer. Other studies had indicated that zoledronic acid (a bone density-enhancing bisphosphonate) may also prevent bone tumors in various metastatic cancers, including metastatic breast cancer. Its role in early stage breast cancer, however, isn’t clear. The headline and lead muddled the main conclusion of the study: that zoledronic acid failed to provide any benefit in the study population as a whole, and the story gave too much weight to a subgroup analysis indicating that the drug does extend life among women with established menopause. Even when they are pre-planned, as in this study, subgroup analyses are difficult to interpret—since they involve only a portion of study subjects. The story also failed to tell readers about some serious adverse events, including bone disease in the jaws of some women in this trial.
Zoledronic acid and other bisphosphonates have been employed as treatments for osteoporosis and to prevent skeletal complications among women with metastatic breast cancer. However, their role in the prevention of recurrence among women with early stage breast cancer isn’t clear.
Animal studies suggest that bisphosphonates may have direct anti-tumor effects in bone. Proponents of zoledronic acid believe it may provide a significant advantage for women with early stage breast cancer—in terms of recurrence and survival. But the results of studies in humans have been contradictory.
A large randomized controlled trial from Austria (the ABCSG-12 trial) published in 2009 suggested that the addition of three years of zoledronic acid to hormonal therapy following surgery for early stage breast cancer provided a 32% advantage in disease-free survival, compared to subjects who did not receive this drug. All the women in the ABCSG-12 trial had chemically induced menopause.
The AZURE trial attempted to confirm the benefits of zoledronic acid in a different study population, one that included both premenopausal and postmenopausal women with early stage breast cancer.
AZURE and other trials are important not only to assess any benefits of zoledronic acid but also to study its adverse effects—which include the potentially devastating side-effect of osteonecrosis of the jaw bone.
We won’t require a discussion of costs in this story because the use of zoledronic acid for early stage breast cancer is still up in the air. However, since the drug is already being sold for other indications, the story would have been better if it had told readers something about the costs of using the drug for approved indications.
The story headline and lead muddled the main conclusion of the AZURE trial: that there was no survival benefit to adding zoledronic acid to standard therapy for women with early stage breast cancer. In contrast to the headline of this story saying that any benefit to younger women is “in question,” the other story we reviewed included a quote from the lead author of the study article saying that not only did younger patients get no benefit, “If anything, they are doing a little bit worse.” The story did accurately report that there may be some benefit to postmenopausal women, but the story should have been more cautious in presenting the results of the sub-group analysis. Overall, the thrust of the story didn’t appear to match the negative results that researchers reported.
The article did not mention any adverse effects associated with zoledronic acid. The story should have at least discussed the incidence of osteonecrosis of the jaw bone—a serious complication affecting more than one percent of study subjects. The article never mentioned that roughly one percent of women taking zoledronic acid in this trial developed a serious side effect: confirmed osteonecrosis of the jawbone. And another half a percent of subjects may have developed this bone-destroying problem. Women weighing the pros and cons of zoledronic acid for early breast cancer—or for other indications such as metastatic breast cancer—would certainly want to take this potentially devastating side-effect into account in their decision-making. And it deserved mention in the article.
The article provided an adequate description of the randomized trial. In addition, it offered readers background on an earlier trial, highlighting some possible reasons that trial produced different results. However, it appeared to overstate the power of a subgroup analysis to produce conclusive results; in this case that the drug may extend the lives of women with established menopause. To produce strong take-home messages, the results of subgroup analyses have to be tested in further clinical trials. The story did offer a statement from an independent expert to this effect further down the page—but never explicitly stated that subgroup analyses have inherent limitations.
There was no hint of disease mongering in this article.
The article used an independent source. Howeever, it failed to tell readers about the support provided by the pharmaceutical company that markets this drug or about speaker fees paid to the lead researcher.
The story did point out that the women in this trial did receive standard therapy, though it did not specifically say what that treatment entails. We will give the story a satisfactory rating since it is not clear that there is a proven alternative that would provide the type of recurrence and survival benefits seen in a previous study of zoledronic acid for early stage breast cancer.
The article did not clarify the regulatory status of zoledronic acid. The FDA has approved zoledronic acid as a treatment for metastatic breast cancer but not for early stage breast cancer.
The article made it clear that zoledronic acid is already being used in routine clinical care for other indications.
The article did not appear to be overly reliant on a news release.