Stephanie Fox-Rawlings, PhD, National Center for Health Research, February 27, 2019
Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Stephanie Fox-Rawlings. Our center analyzes scientific and medical data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug or medical device companies, so I have no conflicts of interest.
We all agree that patients with relapsed refractory multiple myeloma need more treatment options, especially options that work by new mechanisms. Unfortunately, selinexor has serious risks that can cause death. It’s crucial to determine the size of the benefit because of the known risks. It is essential to determine if the benefits outweigh the risks for most patients. At this point we lack the information needed for patients and their doctors to make informed decision about whether to try this new drug.
Let’s consider the risks. All patients in the STORM trial suffered an adverse event, almost all suffered a severe adverse event caused by the drug, and 58% experienced a serious adverse event. 9% of the patients taking the drug died due to an adverse event. Even if many of the adverse events are manageable, they often harm patients’ quality-of-life.
These side effects and even risk of death may be acceptable to some patients – if the drug can help them live longer. But, if the drug cannot provide a meaningful benefit, these risks are not worth it.
The single-arm, open-label study found that 25% of patients responded to the drug, based on a biomarker response. But because this is a single arm trial, there is no controlling for unique aspects of these particular patients. Moreover, the 25% response rate when given with an older drug, dexamethasone, is very similar to the response rate of that older drug alone. So, it is not possible to determine what effect, if any, selinexor has.
It is difficult if not impossible to compare the results of the combination of the new and old drug to just the old drug alone, since the clinical trials included different patients and the available treatments and practice of medicine changed over time.
I’m very glad that the sponsor has already begun a randomized, controlled trial. Some of the results are expected at the end of the year. This should provide much needed information about efficacy.
In addition, it is important to evaluate outcomes that affect patients’ health and quality of life, and not just consider surrogate endpoints.
The trial that we are discussing today (STORM) and the randomized study (BOSTON) focus on surrogate endpoints – overall-response rate and progression-free survival. These don’t directly tell us anything about the impact the new drug has on patients’ lives.
Surrogate endpoints are even more of a problem in studying this drug because the drug itself increases the risk for death. A previous clinical trial compared this drug against physician choice of other drugs for patients with relapsed or refractory AML. It found better remission rates but patients did not live longer. In fact, there was a trend for a shorter life.
Similarly, in the current trial, there was no improvement in quality-of-life due to the drug.
In summary, this drug has serious risks, and we don’t know if it works. How can patients and doctors weigh the ratio of risks to benefits when the risks are serious and there are health benefits are unknown?
I respectfully urge you to tell the FDA to wait until the randomized trial is analyzed to make a decision. While patients need new treatments, they need new treatments to help them live longer or have a better quality of life.
The Oncologic Drugs Advisory Committee voted 8 to 5 to wait until data from the randomized controlled trial was available to make a decision about approval.
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