Indirect Treatment Comparison (ITC) of Mirdametinib and Selumetinib for the Treatment of Children with Neurofibromatosis Type 1-Associated Plexiform Neurofibromas (NF1-PN)
Author(s)
Isha Mol, BSc, MSc1, Timothy Bell, MHA2, Yannan Hu, PhD1, Abraham Langseth, PhD2, Michael Weber, PharmD2, Hoora Moradian, PhD3;
1Cytel, Rotterdam, Netherlands, 2SpringWorks Therapeutics, Inc, Stamford, CT, USA, 3Cytel, Vancouver, BC, Canada
1Cytel, Rotterdam, Netherlands, 2SpringWorks Therapeutics, Inc, Stamford, CT, USA, 3Cytel, Vancouver, BC, Canada
Presentation Documents
OBJECTIVES: To evaluate efficacy and safety outcomes utilizing ITC in children with NF1-PN treated with mirdametinib (MIRDA) vs selumetinib (SELU).
METHODS: Unanchored matching-adjusted indirect comparison (MAIC) and simulated treatment comparison (STC) analyses evaluated outcomes of MIRDA (ReNeu; NCT03962543) vs SELU (SPRINT; NCT01362803), where feasible.
RESULTS: Mean best percent reduction from baseline in target PN volume by blinded independent central review (BICR) was significantly greater with MIRDA vs SELU (MAIC: -36.0% vs -22.8%; STC: -36.2% vs -22.8%). The mean best percent reduction from baseline difference (95% CI) in the MAIC was -13.2% (-22.4%, -4.1%; P=.005; effective sample size [ESS]=54); in the STC was -13.4% (-22.2%, -4.4%; P=.004; N=54). In the MAIC and/or STC, all-grade treatment-related adverse event (TRAE) rates were significantly lower with MIRDA vs SELU for dermatitis acneiform, diarrhea, nausea, vomiting, fatigue, blood creatinine phosphokinase increase, dry skin, pruritus, constipation, abdominal pain, stomatitis, hair color change, headache, and neutrophil count decrease (P<.05). Rate of dose reductions due to TRAEs was significantly lower with MIRDA vs SELU (MAIC: 12% vs 28%, odds ratio [OR]=.355, P=.048; STC: 11% vs 28%, OR=.309, P=.028). Differences in confirmed objective response rate by BICR (MAIC: 51.3% vs 44%, ESS=21; STC: 55.5% vs 44%; N=56) and rates of all-grade paronychia (MAIC/STC: 30% vs 42%), white blood cell count decrease (MAIC: 6% vs 14%; STC: 5% vs 14%), alopecia (MAIC/STC: 13% vs 8%), and asymptomatic ejection fraction decrease (MAIC: 20% vs 14%; STC: 18% vs 14%) were not significantly different between MIRDA vs SELU. Study limitations include possible confounding of unmeasured treatment effect modifiers.
CONCLUSIONS: MIRDA demonstrated a significantly greater mean best percent reduction from baseline in target PN volume, lower rate of dose reductions due to TRAEs, and lower rates of most TRAEs vs SELU in children with NF1-PN. None of the analyses conducted significantly favored SELU.
METHODS: Unanchored matching-adjusted indirect comparison (MAIC) and simulated treatment comparison (STC) analyses evaluated outcomes of MIRDA (ReNeu; NCT03962543) vs SELU (SPRINT; NCT01362803), where feasible.
RESULTS: Mean best percent reduction from baseline in target PN volume by blinded independent central review (BICR) was significantly greater with MIRDA vs SELU (MAIC: -36.0% vs -22.8%; STC: -36.2% vs -22.8%). The mean best percent reduction from baseline difference (95% CI) in the MAIC was -13.2% (-22.4%, -4.1%; P=.005; effective sample size [ESS]=54); in the STC was -13.4% (-22.2%, -4.4%; P=.004; N=54). In the MAIC and/or STC, all-grade treatment-related adverse event (TRAE) rates were significantly lower with MIRDA vs SELU for dermatitis acneiform, diarrhea, nausea, vomiting, fatigue, blood creatinine phosphokinase increase, dry skin, pruritus, constipation, abdominal pain, stomatitis, hair color change, headache, and neutrophil count decrease (P<.05). Rate of dose reductions due to TRAEs was significantly lower with MIRDA vs SELU (MAIC: 12% vs 28%, odds ratio [OR]=.355, P=.048; STC: 11% vs 28%, OR=.309, P=.028). Differences in confirmed objective response rate by BICR (MAIC: 51.3% vs 44%, ESS=21; STC: 55.5% vs 44%; N=56) and rates of all-grade paronychia (MAIC/STC: 30% vs 42%), white blood cell count decrease (MAIC: 6% vs 14%; STC: 5% vs 14%), alopecia (MAIC/STC: 13% vs 8%), and asymptomatic ejection fraction decrease (MAIC: 20% vs 14%; STC: 18% vs 14%) were not significantly different between MIRDA vs SELU. Study limitations include possible confounding of unmeasured treatment effect modifiers.
CONCLUSIONS: MIRDA demonstrated a significantly greater mean best percent reduction from baseline in target PN volume, lower rate of dose reductions due to TRAEs, and lower rates of most TRAEs vs SELU in children with NF1-PN. None of the analyses conducted significantly favored SELU.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO122
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
SDC: Neurological Disorders, SDC: Oncology, SDC: Pediatrics, SDC: Rare & Orphan Diseases