Interpreting MEK Inhibitor Clinical Trial Data and Assessing Treatment Response in NF1-PN

In this segment, the physicians examine how clinical trial data for MEK inhibitors translate into everyday practice. They discuss findings from key studies—including the ReNeu (mirdametinib), SPRINT and KOMET (selumetinib) trials—which reported variable volumetric response rates in both children and adults. One physician notes that these studies relied on 3D volumetric MRI measurements, a technique that is rarely available in routine clinical settings, making direct replication of trial results challenging. He explains that this limitation contributes to wide variability in reported response rates, even including unexpected placebo “shrinkage” observed in KOMET. Because volumetrics cannot be consistently applied, the physicians emphasize that clinicians must prioritize symptoms, functional impact, and quality-of-life improvements—especially changes in pain—when judging treatment benefit. They caution against interpreting one MEK inhibitor as superior to another based solely on trial data, concluding instead that both selumetinib and mirdametinib offer meaningful responses and should be selected based on tolerability and patient needs.