NF1 With PNs: Future of Treatment With MEK Inhibitors

Kaleb H. Yohay, MD: In patients with neurofibromatosis type 1 [NF1] being treated for the plexiform neurofibromas with MEK inhibitors and selumetinib, in addition to reduction in the size of tumors, we’re often seeing pain relief that’s starting quite soon after initiation of treatment. We’re also seeing changes and improvement in neurological function, such as strength, gait, and other things that might have been impacted by the plexiform neurofibroma.

The recent positive results of the clinical trials using MEK inhibitors and selumetinib are changing the way we think about treating neurofibromatosis. In the past, there have not been any disease-modifying therapies for NF1. With the availability of MEK inhibitors and selumetinib—along with the data from the clinical trials suggesting that the majority of patients show some benefit—we are starting to treat many more patients medically prior to thinking about surgical treatment. We are able to give our patients options about how to approach treatment of their tumors. It also offers the possibility of treating tumors that we wouldn’t have had any options for before when they were not surgically approachable.

For the approval of selumetinib for the use of treatment of plexiform neurofibromas, the specific indication will be for children aged 3 to 18 with NF1 and an inoperable symptomatic plexiform neurofibroma. That will probably be the first population of patients that will be treated with selumetinib. There are thoughts that selumetinib and other MEK inhibitors may have the potential for additional therapeutic uses outside that age window; for instance, adults with plexiform neurofibromas or children under age 3. Additionally, patients who are experiencing pain because of plexiform neurofibromas, even if it is operable, might also be considered for a treatment with these medications.

There are also thoughts that these medications may be helpful for other symptoms associated with neurofibromatosis type 1, and there are a number of clinical trials being considered to look at the use of selumetinib as well as other MEK inhibitors for the treatment of things such as cutaneous neurofibromas. There already are clinical trials for optic pathway gliomas and possibly future clinical trials for cognitive impairment in neurofibromatosis. The potential use for these drugs can be quite broad, though the initial indication will be more limited.

At this point, it remains to be seen who are the optimal patients to offer treatment with MEK inhibitors and what the right timing is, to be honest. We are still in the process of determining whether being proactive and treating tumors while they are small and presymptomatic is better than waiting until they are larger and causing neurological impairment, functional impairment, or other symptoms. It will take some time using these medications in a variety of patients before we fully understand how to stratify patients in terms of which ones undergo therapy and which ones wait.

Why would we treat with MEK inhibitors or selumetinib rather than just treat symptoms? Our hope in using these medications is that we actually modify the course of the disease, reducing the growth of tumors, reducing the potential threat these tumors might cause to surrounding structures, in addition to treating the symptoms.

The approval of a medication that is specifically indicated for patients with neurofibromatosis and plexiform neurofibromas is having a tremendous impact on the patient population as well as clinicians caring for these patients. I’ve been taking care of patients with NF1 for about 20 years, and the approval of these medications is already totally changing the conversations I have with families about the disease, the future, and what to hope for. In the past, we have been limited to treating symptoms or recommending surgery. To have a medication that can slow, stop, or even reduce tumor growth in these patients, I think the impact is unlimited in many ways. The hope that it brings to the families we take care of is tremendous.