NFS-18. Lower Body Surface Area is Associated with Increased Likelihood of Plexiform Neurofibroma Response to MEK Inhibition

Abstract

BACKGROUND: MEK inhibitors (MEKi) are altering the management approach for plexiform neurofibroma (PN), with high rates of treatment response to multiple MEKi. Despite these successes, a subset of PN fail to respond and little is known about the clinical features associated with treatment response. METHODS: We performed a retrospective cohort study integrating clinical trial data (NCT01362803, NCT02407405, NCT02096471, NCT03231306, NCT03363217) to identify baseline clinical features associated with response of PN to MEKi. Partial response (PR) was defined as ≥20 percent reduction in tumor volume from baseline. RESULTS: Of 232 eligible participants, adequate clinical trial and imaging data was available for 223 participants. In the primary analysis of 184 participants with central response evaluation, the median age was 15.2 years with a median tumor volume of 488 milliliters at clinical trial enrollment. One hundred and eighteen (64%) participants achieved a PR with median time to PR of 8 cycles. Thirty-five participants (19%) required a dose reduction prior to 6 cycles of therapy due to toxicity. Younger age and lower body surface area (BSA) were significantly associated with PR in univariate analysis while female sex and typical PN appearance (versus nodular) on imaging approached significance. In multivariable analysis, only lower BSA was significantly associated with response while typical PN appearance approached significance. In the multivariable analysis of pediatric participants treated per BSA-based dosing, lower BSA was the only feature significantly associated with PR. In the expanded analysis of all 223 participants, lower BSA and typical PN appearance were significantly associated with PR. CONCLUSION: Lower BSA and typical appearance of PN were associated with PR to MEK inhibitors. Future studies of MEK inhibitor for PN should integrate tumor pharmacokinetic-pharmacodynamic analyses to prospectively explore the impact of BSA on treatment response.