Herbert B. Newton, MD, FAAN: In terms of what some of the unmet needs are for patients with NF1 [neurofibromatosis type 1] and plexiform neurofibromas, it’s important that we find additional chemotherapy options for these patients that have symptomatic and inoperable plexiform tumors. Selumetinib is the first drug that’s been proven to have efficacy, but we need newer agents with increased efficacy and activity with reduced toxicity and more durable responses. This would mean third- and fourth-generation MEK inhibitors as well as other types of signal transduction inhibitors that can slow down tumor growth.
Kaleb H. Yohay, MD: Neurofibromatosis affects so many aspects of life for our patients, and there are so many unmet needs, even with the advent of these drugs. The use of MEK inhibitors and selumetinib in treating plexiform neurofibromas is a huge first step, but there are a number of other symptoms that are just as important to the patient population, in terms of looking for disease-modifying therapy. In particular, cutaneous neurofibromas—which are neurofibromas on the skin—can be very disfiguring. They are not as medically harmful as the plexiform neurofibromas but have tremendous impact on patients in terms of their social lives, ability to get jobs, and have a wide array of effects on quality of life for these patients.
Additionally, problems with learning, attention, and anxiety are very common and prevalent in this population and similarly can have a large impact on the lives of our patients. There are currently no medications specifically indicated for treatment in adults or children with NF1 with behavior or learning issues. Another unmet need in this patient population is we don’t know a good way to treat malignant peripheral nerve sheath tumors [MPNSTs]. There is an increased rate of this type of sarcoma developing in patients with NF1. These tumors are highly aggressive, very difficult to treat, and don’t respond well to traditional chemotherapy or radiation. We are in desperate need of better therapies for treatment of MPNST as well as other cancer types that can be associated with NF1.
Herbert B. Newton, MD, FAAN: What advice might I have for physicians treating patients with NF1 and plexiform neurofibromas? I think they need to be aware of selumetinib as an option now for these patients. Especially with symptomatic plexiform neurofibromas that cannot undergo a quality tumor resection, they now have a drug option that can actually shrink these tumors in two-thirds of cases and give symptomatic relief, especially in patients who have pain and disfigurement.
Caregivers should also be familiar with selumetinib as a viable drug option for their loved ones, and their NF [neurofibromatosis] treatment team should be aware of this drug. They need to know the symptoms and aspects of plexiform tumors. It can be helpful for this drug to be used as treatment, and they should bring this up with their team.
Kaleb H. Yohay, MD: NF1 is a very complex disorder, and the treatment decisions and management of these patients is dependent on familiarity with the disease and the disease population. One of my primary recommendations for clinicians taking care of adults and children with NF1 is, when possible, to refer to centers where they are treating a large number of these patients and have great familiarity with the available treatments, as well as the various signs and symptoms and management of neurofibromatosis.
Additionally, a number of guidelines have been recently published. There have been recent updated guidelines for the treatment and management of children with NF1, as well as for the first time, management guidelines for treatment of adults with NF1. These guidelines can be helpful tools for clinicians in knowing what aspects of neurofibromatosis they need to be monitoring on a regular basis and how to approach diagnosis and management of a variety of signs and symptoms associated with NF1.
One of the most difficult aspects of neurofibromatosis is the wide variety of signs and symptoms that can be associated with the disorder. For parents of children with NF1, this can be particularly challenging because it can be really hard to know what symptoms are attributable to NF1 specifically and what are things typically associated with childhood and typical childhood illnesses. For parents of children with NF1, we recommend that they seek out the care of clinicians that are really familiar with NF1 to help guide them through the entire life span of their child and knowing which symptoms to be cognizant of. This is because at every age there are different things, different aspects of this disorder that parents need to watch for.
Additionally, I’m always talking with families about the importance of educating themselves about NF1 and the different manifestations of the disorder. This is in part because frequently there are times when they will encounter clinicians or the health care system in such a way that they may be the best-educated person in the room about this disorder. They can bring knowledge and understanding of NF1 to their health care providers and be an active participant in the choices that need to be made about the health care of their children.
This is a very exciting time to be involved in the care of people who have neurofibromatosis type 1, and we’re really on the cusp of a totally different world for these patients. We’ve never had a disease-modifying therapy available, and I think the availability of these types of medications is going to transform how we take care of adults and children with neurofibromatosis. They give us more options for treatment but also impact how we screen patients to look for tumors. They impact where we want to be taking care of these patients, so that they can have availability for the best and latest treatment, as well as appropriate monitoring for the adverse effects for treatment. I also think it will change how parents and families with family members with neurofibromatosis need to be educated about the disorder, so they can let their care providers know about the availability of new treatments, because that may not be generally known amongst clinicians. While there is still a lot to be learned about how to use these medications, they are going to be transformative in how we treat people with NF1.