Stephanie Fox-Rawlings, PhD, National Center for Health Research, December 18, 2019
Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Stephanie Fox-Rawlings, the Center’s Research Manager. 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 can all agree that there is a need for better treatment options for patients with epithelioid sarcoma. We can also agree that new treatments still need to have a real and meaningful benefit to patients. Just as important, there needs to be enough information about this treatment option so that patients and their physicians can determine if the benefits outweigh the risks for each patient, so they can decide whether or not to try it. There can be differences of opinion on what would be a meaningful benefit and what is a likely risk, and those will vary for individual patients.
Unfortunately, there is limited information about the benefits of tazemetostat. There is only one clinical trial with 2 cohorts that have different eligibility criteria and different primary endpoints. Only 11% to 15% of the patients in those cohorts had a decrease in the size of lesions with variation in time to response and duration of response.
Based on the data discussed today, it is difficult to determine how well the treatment works and whether its effect is clinically meaningful. A major problem is the lack of a good control group. In this study, there was no internal comparison group and the options for historical controls that were provided differed from the current study in terms of patient selection, study design, measurement of response rate, and/or when the study occurred. In other words, the control groups were different enough that they are not very informative.
Another major problem is that the study doesn’t provide any information about patient survival or quality of life. A decrease in tumor size is desirable, but it may not be meaningful for patients if it isn’t associated with better quality of life or long-term prognosis. So the level of benefit that patients receive from a decrease in tumor size is unclear.
Unfortunately, there are a lot of adverse events associated with this drug. Some adverse events were serious, including the potential for secondary cancers. But, many of the less serious adverse events are also likely to reduce a patient’s quality of life. These risks may be acceptable for some patients if the treatment provided a meaningful benefit. The purpose of today’s meeting is to weigh those likely risks compared to the benefit of tumor shrinkage for only 11-15% of the patients.
Some might say that since the current treatment options are poor, any new treatment should be approved even if it only provides hope. But if the mission of the FDA was merely to provide hope, they would need to approve placebos as well as every new drug. FDA needs to maintain high standards of approval. This Advisory Committee is asked to advise the FDA if there is sufficient scientific evidence that the benefits outweigh the risks for most patients or if not, if there a proven subgroup of patients that the drug could be approved for. If you can’t conclude that benefits outweigh the risks for a defined group of patients,please consider advising FDA about the kind of data are needed to provide that evidence PRIOR to approval. It can be harder to get this data after approval.
The Oncologic Drugs Advisory Committee voted 11 to 0 in favor of approval of tazemetostat for the treatment of patients with metastatic or locally advanced epithelioid sarcoma not eligible for curative surgery. You can read more about the meeting here.