MATCHING-ADJUSTED INDIRECT COMPARISON OF ZURLETRECTINIB VERSUS FIRST-GENERATION TRK INHIBITORS IN NTRK FUSION-POSITIVE SOLID TUMORS
Author(s)
Ying Chen, MD, Bin Wu, PhD, MD.
Shanghai Chest Hospital, Shanghai, China.
Shanghai Chest Hospital, Shanghai, China.
OBJECTIVES: To compare the efficacy and safety of zurletrectinib (ICP-723) with first-generation TRK inhibitors, entrectinib and larotrectinib, in patients with NTRK fusion-positive advanced solid tumors, in the absence of head-to-head trials.
METHODS: Individual patient data for zurletrectinib were pooled from two prospective studies (ICP-CL-00501 and ICP-CL-00505; n=55; data cutoff, 31 July 2025). Aggregate comparator data were taken from a published indirect comparison of adult patients with NTRK fusion-positive advanced solid tumors excluding primary CNS tumors (entrectinib, n=74; larotrectinib, n=117). Unanchored matching-adjusted indirect comparisons (MAIC) reweighted zurletrectinib patients to match comparator baseline characteristics, including sex, age, brain metastases, ECOG status, selected tumor types, and NTRK fusion subtype. Binary outcomes were compared using rate differences (RDs). Progression-free survival (PFS) and overall survival (OS) were analyzed using digitized Kaplan-Meier data and weighted Cox models.
RESULTS: After matching, effective sample sizes were 20.2 for the entrectinib comparison and 21.5 for the larotrectinib comparison. Treatment with zurletrectinib showed a higher objective response rate than entrectinib (94.6% vs 63.5%; RD, 31.1%; 95% CI, 16.3%-45.8%; P < 0.0001) and larotrectinib (94.0% vs 65.0%; RD, 29.0%; 95% CI, 15.7%-42.2%; P < 0.0001). Compared with entrectinib, zurletrectinib was associated with longer PFS (median, 34.0 vs 10.8 months; HR, 0.19; 95% CI, 0.07-0.52) and OS (HR, 0.12; 95% CI, 0.03-0.41). Compared with larotrectinib, PFS was similar (median, 34.0 vs 33.4 months; HR, 0.62; 95% CI, 0.30-1.32; P=0.22), while OS favored zurletrectinib (HR, 0.24; 95% CI, 0.07-0.85). Serious treatment-related adverse events were 5.6% vs 10.0% and 5.4% vs 5.4%; treatment-related discontinuations were 0.0% vs 4.0% and 0.0% vs 0.7%.
CONCLUSIONS: In this unanchored MAIC, zurletrectinib was associated with higher response rates than entrectinib and larotrectinib, improved survival outcomes versus entrectinib, and comparable safety. Findings should be interpreted considering residual confounding and reduced effective sample size.
METHODS: Individual patient data for zurletrectinib were pooled from two prospective studies (ICP-CL-00501 and ICP-CL-00505; n=55; data cutoff, 31 July 2025). Aggregate comparator data were taken from a published indirect comparison of adult patients with NTRK fusion-positive advanced solid tumors excluding primary CNS tumors (entrectinib, n=74; larotrectinib, n=117). Unanchored matching-adjusted indirect comparisons (MAIC) reweighted zurletrectinib patients to match comparator baseline characteristics, including sex, age, brain metastases, ECOG status, selected tumor types, and NTRK fusion subtype. Binary outcomes were compared using rate differences (RDs). Progression-free survival (PFS) and overall survival (OS) were analyzed using digitized Kaplan-Meier data and weighted Cox models.
RESULTS: After matching, effective sample sizes were 20.2 for the entrectinib comparison and 21.5 for the larotrectinib comparison. Treatment with zurletrectinib showed a higher objective response rate than entrectinib (94.6% vs 63.5%; RD, 31.1%; 95% CI, 16.3%-45.8%; P < 0.0001) and larotrectinib (94.0% vs 65.0%; RD, 29.0%; 95% CI, 15.7%-42.2%; P < 0.0001). Compared with entrectinib, zurletrectinib was associated with longer PFS (median, 34.0 vs 10.8 months; HR, 0.19; 95% CI, 0.07-0.52) and OS (HR, 0.12; 95% CI, 0.03-0.41). Compared with larotrectinib, PFS was similar (median, 34.0 vs 33.4 months; HR, 0.62; 95% CI, 0.30-1.32; P=0.22), while OS favored zurletrectinib (HR, 0.24; 95% CI, 0.07-0.85). Serious treatment-related adverse events were 5.6% vs 10.0% and 5.4% vs 5.4%; treatment-related discontinuations were 0.0% vs 4.0% and 0.0% vs 0.7%.
CONCLUSIONS: In this unanchored MAIC, zurletrectinib was associated with higher response rates than entrectinib and larotrectinib, improved survival outcomes versus entrectinib, and comparable safety. Findings should be interpreted considering residual confounding and reduced effective sample size.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO18
Topic
Clinical Outcomes, Health Policy & Regulatory, Health Technology Assessment
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Oncology