464P Intra-patient (Pt) comparison from larotrectinib (Laro) clinical trials in tropomyosin receptor kinase (TRK) fusion cancer: An expanded dataset

Abstract

Laro, a highly selective, central nervous system (CNS)-active TRK inhibitor approved for adult and paediatric pts with TRK fusion cancer, showed rapid and durable responses in three phase I/II single-arm studies. The growth modulation index (GMI) is an intra-pt comparison that compares progression-free survival (PFS) on current therapy against time to progression or treatment failure (TTP) on most recent prior therapy. A GMI ratio ≥1.33 is a threshold for meaningful clinical activity. We report the GMI of 140 laro-treated pts with an extended follow-up, and of an expanded dataset with an additional 36 pts (176 pts in total) to assess the treatment effect of laro more extensively in pts with non-primary CNS TRK fusion cancer previously treated with ≥1 line of therapy. Adult and paediatric pts treated in three laro clinical trials (NCT02576431, NCT02122913, and NCT02637687) were analysed retrospectively. TTP on prior line of therapy was investigator-assessed. PFS on laro was determined by an independent review committee (RECIST v1.1). Pts without progression were censored as of last visit. Median GMI, TTP, and PFS were estimated by Kaplan–Meier analyses. Data cut-off: July 2021. GMI results are shown in the table for the 140 pts with extended follow-up and the expanded dataset of 176 pts. Of the 53 pts with a GMI <1.33 in the expanded dataset, 10 were censored and continuing treatment. Of pts with 1, 2, or ≥3 prior lines of therapy, 47 (69%), 29 (59%), and 47 (80%) pts, respectively, had a GMI of ≥1.33 on laro. Median TTP on prior therapy was 3.0 months. Median PFS on laro was 19.6 months.Table: 464PLaro-treated pts (N)Data cut-offGMI≥1.33,n (%)≥1 to <1.33,n (%)<1,n (%)Median(95% CI)140 (Extended follow-up)July 2020 (Italiano et al, ASCO 2021)103 (74)7 (5)30 (21)8.9(6.2–17.4)July 2021105 (75)6 (4)29 (21)7.9(5.8–11.7)176 (Expanded dataset)July 2021123 (70)9 (5)44 (25)7.2(5.5–10.0) Open table in a new tab With extended follow-up, 75% of laro-treated pts with TRK fusion cancer had prolonged PFS compared with most recent prior therapy, irrespective of the number of prior lines of therapy received. This reinforces the benefits of using laro to treat pts with TRK fusion cancer.