Larotrectinib versus prior therapies in tropomyosin receptor kinase fusion cancer: An intra-patient comparative analysis

Antoine Italiano, Shivani Nanda, Andrew Briggs, Jesus Garcia-Foncillas, Ulrik Lassen, Gilles Vassal, Shivaani Kummar, Cornelis M. van Tilburg, David S. Hong, Theodore W. Laetsch, Karen Keating, John A. Reeves, Marc Fellous, Barrett H. Childs, Alexander Drilon, David M. Hyman

Research output: Contribution to journalArticlepeer-review

Abstract

Randomized controlled basket trials investigating drugs targeting a rare molecular alteration are challenging. Using patients as their own control overcomes some of these challenges. Growth modulation index (GMI) is the ratio of progression-free survival (PFS) on the current therapy to time to progression (TTP) on the last prior line of therapy; GMI ≥ 1.33 is considered a threshold of meaningful clinical activity. In a retrospective, exploratory analysis among patients with advanced tropomyosin receptor kinase (TRK) fusion cancer treated with the selective TRK inhibitor larotrectinib who received ≥1 prior line of therapy for locally advanced/metastatic disease, we determined the proportion of patients with GMI ≥ 1.33; patients who had not progressed by data cut-off were censored for PFS. Among 72 eligible patients, median GMI was 2.68 (range 0.01–48.75). Forty-seven patients (65%) had GMI ≥ 1.33; 13/25 patients (52%) with GMI < 1.33 had not yet progressed on larotrectinib. Kaplan–Meier estimates showed a median GMI of 6.46. The probability of attaining GMI ≥ 1.33 was 0.75 (95% confidence interval (CI), 0.65–0.85). Median TTP on previous treatment was 3.0 months (95% CI, 2.6–4.4). Median PFS on larotrectinib was not estimable ((NE); 95% CI, NE; hazard ratio, 0.220 (95% CI, 0.146–0.332)). This analysis suggests larotrectinib improves PFS for patients with TRK fusion cancer compared with prior therapy.

Original languageEnglish (US)
Article number3246
Pages (from-to)1-10
Number of pages10
JournalCancers
Volume12
Issue number11
DOIs
StatePublished - Nov 2020

Keywords

  • Growth modulation index
  • Larotrectinib
  • NTRK gene fusion
  • TRK fusion cancer
  • Tropomyosin receptor kinase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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