Dr McNall-Knapp on the Efficacy of MEK Inhibition in NF1-Associated PNs

“If [a patient is] dealing with pain, or you’re trying to keep the tumor from growing and being life threatening, these drugs are wonderful. They’ve [been shown to] quickly help with pain and [other] symptoms. [However], if [the challenges the patient is] dealing with are mostly cosmetic, these drugs can be disappointing. You don’t get quite the shrinkage you would hope to see [based on] some pictures in the publications.”

Rene Y. McNall-Knapp, MD, a pediatric hematologist-oncologist at the Jimmy Everest Center at Oklahoma Children’s Hospital Oklahoma University Health, discussed the benefits and limitations of MEK inhibitors for the treatment of pediatric and adult patients with neurofibromatosis type 1 (NF1)–associated plexiform neurofibromas (PNs).

Therapeutic prospects for patients with NF1-associated PNs improved in 2020, when the MEK1/2 inhibitor selumetinib (Koselugo) received FDA approval for pediatric patients with symptomatic, inoperable PNs, becoming the first agent to demonstrate clinically meaningful benefit in this population, McNall-Knapp began. However, the pediatric‑only label for selumetinib created a coverage gap: insurers often denied access to this agent for adults in this population, she noted. Most recently, in February 2025, the FDA approved the second‑generation MEK inhibitor mirdametinib (Gomekli) for the treatment of both pediatric and adult NF1‑associated PN populations. 

Different MEK inhibitors offer similar therapeutic values, such as halting tumor growth and rapidly reducing PN‑related pain, functional limitations, and other morbidities, McNall-Knapp said.

Additionally, a proportion of treated patients achieve radiographic shrinkage, although dramatic regressions comparable with images reported in peer-reviewed journals remain uncommon in routine practice, she explained. Consequently, expectations regarding the benefits of these agents should be adjusted depending on treatment goals, McNall-Knapp stated. MEK inhibition is highly effective for symptom control and disease stabilization, but less reliable for purely cosmetic debulking, she summarized.

NF1-associated PNs are also a heterogeneous disease, according to McNall-Knapp. Lesions may encircle major airways or compress pelvic organs, rendering resection impossible, she stated. In such settings, these therapies are invaluable, although patients seeking aesthetic improvement may be disappointed by limited volumetric change, she concluded.