The Potential Long-Term Comparative Effectiveness of Larotrectinib vs Repotrectinib for Treatment of NTRK Gene Fusion-Positive Cancers
Author(s)
Kangho Suh, PharmD, PhD1, Ashley Kang, BA, MPH2, Jamie Grossman, PhD3, Sreevalsa Appukkuttan, MPH3, Sean D. Sullivan, PhD4.
1Assistant Professor, University of Pittsburgh, Pittsburgh, PA, USA, 2Curta, Inc., Seattle, WA, USA, 3Bayer US LLC, Whippany, NJ, USA, 4University of Washington, Seattle, WA, USA.
1Assistant Professor, University of Pittsburgh, Pittsburgh, PA, USA, 2Curta, Inc., Seattle, WA, USA, 3Bayer US LLC, Whippany, NJ, USA, 4University of Washington, Seattle, WA, USA.
Presentation Documents
OBJECTIVES: The treatment of neurotrophic tyrosine kinase (NTRK) gene fusion-positive cancers has seen significant advances with the development of targeted therapies such as the TRK inhibitors larotrectinib and second-generation repotrectinib. Both therapies showed promising efficacy across a range of tumor types in their respective tumor-agnostic basket trials for patients with locally advanced or metastatic NTRK gene fusion-positive cancers. The objective of this study was to extrapolate progression-free survival (PFS) and overall survival (OS) clinical trial results in adult patients (≥18 years old) treated with larotrectinib or repotrectinib to assess expected life-years (LYs) and quality-adjusted life-years (QALYs).
METHODS: We developed a partitioned survival model to project long-term outcomes. Larotrectinib survival data were derived from an updated July 2023 analysis of 215 adults NTRK gene fusion-positive cancers from the larotrectinib clinical trials program (NCT02122913, NCT02637687, and NCT02576431). Repotrectinib survival data were derived from a phase 1/2 study (NCT03093116) of 40 adult patients with NTRK gene fusion-positive cancers with no prior use of TRK inhibitors. PFS and OS for both treatments were estimated using parametric survival distributions (Exponential, Weibull, Log-logistic, and Log-normal), then selected based on goodness-of-fit statistics, visual fit, and clinical plausibility. QALYs were estimated by adjusting the time spent in the pre progression and post progression health states by utility values from the literature.
RESULTS: Exponential curves were used to extrapolate clinical trial results. Treatment with larotrectinib resulted in 5.07 LYs (95% Credible Interval [CrI]: 4.12, 6.21) and 2.87 QALYs (95% CrI: 1.35, 4.95). Relative to repotrectinib, treatment with larotrectinib yielded additional gains of 2.34 LYs and 1.23 QALYs.
CONCLUSIONS: We extrapolated results from clinical studies of larotrectinib and repotrectinib in locally advanced or metastatic NTRK gene fusion-positive cancers in adults. Larotrectinib may produce substantial life expectancy and quality-adjusted life-year gains relative to repotrectinib. Additional data with more mature data will further inform this comparison.
METHODS: We developed a partitioned survival model to project long-term outcomes. Larotrectinib survival data were derived from an updated July 2023 analysis of 215 adults NTRK gene fusion-positive cancers from the larotrectinib clinical trials program (NCT02122913, NCT02637687, and NCT02576431). Repotrectinib survival data were derived from a phase 1/2 study (NCT03093116) of 40 adult patients with NTRK gene fusion-positive cancers with no prior use of TRK inhibitors. PFS and OS for both treatments were estimated using parametric survival distributions (Exponential, Weibull, Log-logistic, and Log-normal), then selected based on goodness-of-fit statistics, visual fit, and clinical plausibility. QALYs were estimated by adjusting the time spent in the pre progression and post progression health states by utility values from the literature.
RESULTS: Exponential curves were used to extrapolate clinical trial results. Treatment with larotrectinib resulted in 5.07 LYs (95% Credible Interval [CrI]: 4.12, 6.21) and 2.87 QALYs (95% CrI: 1.35, 4.95). Relative to repotrectinib, treatment with larotrectinib yielded additional gains of 2.34 LYs and 1.23 QALYs.
CONCLUSIONS: We extrapolated results from clinical studies of larotrectinib and repotrectinib in locally advanced or metastatic NTRK gene fusion-positive cancers in adults. Larotrectinib may produce substantial life expectancy and quality-adjusted life-year gains relative to repotrectinib. Additional data with more mature data will further inform this comparison.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO67
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy, Relating Intermediate to Long-term Outcomes
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Oncology