ID #383 Growth Velocity in Pediatric Patients on Trametinib: A Single-Center Experience

Background

The MAPK inhibitor tovorafenib has been associated with decreased growth velocity in pediatric patient[1]s and whether MEK inhibition produces similar effects remains unclear. We assessed growth patterns in pediatric patients treated with trametinib (MEK inhibitor) at our institute.

Methods

Retrospective review of pediatric patients receiving trametinib at our institute. Height Zscores were collected at baseline and annually while on treatment. Growth velocity was calculated as ΔZ/year. Descriptive statistics and individual growth trajectories were analyzed

Results

Median duration of treatment/follow up was 45.5 months (17-59 months). Among 8 analyzed patients (median age 5.2 years), median ΔZ/year was +0.212 (90% CI 0.086–0.319). Seven patients (87.5%) had ΔZ/year ≥0; one patient showed minimal decline (ΔZ/year −0.008). No patient exhibited clinically meaningful growth deceleration ( > −0.5 ΔZ/year) during Trametinib therapy. All NF1associated cases (5/5) had improvement in their Z scores at median follow up of 47 months.

Conclusion

In our small cohort, trametinib treatment was associated with stable or modestly improved height Z-scores while on treatment, with no signal of growth suppression. This in contrast to significant decline in growth velocity reported with tovorafenib[2]. Larger studies with longer follow-up incorporating standardized endocrine assessment are warranted to further characterize growth outcome in children receiving MEK inhibition.

1. Karen Wright, Cassie Kline, Mohamed Shebl Abdelbaki, Elias Sayour, Erin Crotty, Eric Raabe, Jennifer Elster, Michael Prados, Daphne Haas-Kogan, Sabine Mueller, CTNI-03. DECREASED GROWTH VELOCITY IN A PHASE 1 TRIAL (PNOC014) OF TOVORAFENIB IN PATIENTS WITH RECURRENT OR PROGRESSIVE MAPK-ALTERED TUMORS, Neuro-Oncology, Volume 26, Issue Supplement_8, November 2024, Pages viii94–viii95