MATCHING-ADJUSTED INDIRECT COMPARISON OF LUVOMETINIB VERSUS SELUMETINIB IN THE TREATMENT FOR PEDIATRIC PATIENTS WITH NEUROFIBROMATOSIS TYPE 1 IN CHINA
Author(s)
Chang Luo, MSc1, Lili Cheng, MBA2, Zigang Li, MSc3, Yang Yang, MSc3, Xin Chen, MSc3, Keruo Zhou, MSc3, Shitong Xie, PhD1.
1Tianjin University, Tianjin, China, 2Jiangsu Provincial Pharmacy Association (JPPA), Nanjing, China, 3Shanghai Fosun Pharmaceutical (Group) Co., Ltd., Shanghai, China.
1Tianjin University, Tianjin, China, 2Jiangsu Provincial Pharmacy Association (JPPA), Nanjing, China, 3Shanghai Fosun Pharmaceutical (Group) Co., Ltd., Shanghai, China.
Presentation Documents
OBJECTIVES: Neurofibromatosis type 1 (NF-1) is an autosomal dominant genetic disease that typically presents in early childhood, characterized by café-au-lait macules and multiple neurofibromas. This study aimed to compare the efficacy and safety of luvometinib with selumetinib in pediatric NF-1 patients aged over 2 years through a matching-adjusted indirect comparison (MAIC).
METHODS: A systematic literature review was conducted to identify trial data for selumetinib, with 2 clinical studies identified. As both the luvometinib and selumetinib trials were single-arm and lacked a common comparator, an unanchored MAIC was employed. Individual patient data from a 2-year, phase II trial of luvometinib, NCT04954001 (N=43) were reweighted to match the baseline characteristics from aggregated data from SPRINT (NCT01362803), a 3-year, phase II trial of selumetinib (N=50). Several scenarios were explored in the population adjustment, with different sets of baseline variables included. Investigator-assessed objective response rate (ORR), partial response (PR) rate, progression-free survival (PFS), and treatment-related adverse events (TRAEs) rate with a severity grade ≥ 3 were assessed.
RESULTS: Given inconsistent variable definitions and a low effective sample size (ESS) in other scenarios, population adjustment was performed based on age and sex, with an ESS of 34. The adjusted analysis suggested no significant differences in ORR (ORR difference: -7.8%; p=0.296), PR rate (PR rate difference: -4.4%; p=0.535) and PFS (PFS HR 3.29; 95% CI 0.81-13.37; p=0.096) between treatments. In comparison with selumetinib, luvometinib was associated with a significantly lower rate of certain grade ≥ 3 TRAEs, including diarrhea, dermatitis acneiform, and weight gain, but the rate of folliculitis was significantly higher.
CONCLUSIONS: The MAIC results indicated no significant difference in response or survival outcomes. However, luvometinib demonstrated comparable or superior safety for most grade ≥ 3 TRAEs compared to selumetinib, except for a higher rate of folliculitis.
METHODS: A systematic literature review was conducted to identify trial data for selumetinib, with 2 clinical studies identified. As both the luvometinib and selumetinib trials were single-arm and lacked a common comparator, an unanchored MAIC was employed. Individual patient data from a 2-year, phase II trial of luvometinib, NCT04954001 (N=43) were reweighted to match the baseline characteristics from aggregated data from SPRINT (NCT01362803), a 3-year, phase II trial of selumetinib (N=50). Several scenarios were explored in the population adjustment, with different sets of baseline variables included. Investigator-assessed objective response rate (ORR), partial response (PR) rate, progression-free survival (PFS), and treatment-related adverse events (TRAEs) rate with a severity grade ≥ 3 were assessed.
RESULTS: Given inconsistent variable definitions and a low effective sample size (ESS) in other scenarios, population adjustment was performed based on age and sex, with an ESS of 34. The adjusted analysis suggested no significant differences in ORR (ORR difference: -7.8%; p=0.296), PR rate (PR rate difference: -4.4%; p=0.535) and PFS (PFS HR 3.29; 95% CI 0.81-13.37; p=0.096) between treatments. In comparison with selumetinib, luvometinib was associated with a significantly lower rate of certain grade ≥ 3 TRAEs, including diarrhea, dermatitis acneiform, and weight gain, but the rate of folliculitis was significantly higher.
CONCLUSIONS: The MAIC results indicated no significant difference in response or survival outcomes. However, luvometinib demonstrated comparable or superior safety for most grade ≥ 3 TRAEs compared to selumetinib, except for a higher rate of folliculitis.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
CO74
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
SDC: Oncology, SDC: Pediatrics, SDC: Rare & Orphan Diseases