Abstract CT199: Larotrectinib in TRK fusion cancer patients: Outcomes by prior therapy and performance status
Authors: Drilon Alexander , van Tilburg Cornelis M. , Farago Anna F. , Kummar Shivaani , Berlin Jordan , Albert Catherine M. , McDermott Ray , Lassen Ulrik N. , Reeves John A. , Brega Nicoletta , Childs Barrett H. , Laetsch Theodore W. , Hong David S. 
Published: September 2020

Abstract
Introduction: Larotrectinib, a highly selective Food and Drug Administration- and European Medicines Agency-approved TRK inhibitor, achieved an objective response rate (ORR) of 79% and a median duration of response (DoR) of 35.2 months across various cancers (Hong et al. Lancet Oncol. In press). In this data set, outcomes by the number of lines of prior therapy or baseline performance status have not previously been reported.
Methods: Data were pooled from three clinical trials of patients with TRK fusion cancer treated with larotrectinib (NCT02122913, NCT02576431, NCT02637687). Patients were stratified based on the number of lines of prior therapy (0, 1, 2, or ≥3) and baseline Eastern Cooperative Oncology Group (ECOG) performance status (0, 1, 2, or 3). A post hoc analysis of ORR, assessed by investigators using Response Evaluation Criteria in Solid Tumors 1.1, DoR, progression-free survival (PFS), and overall survival (OS) was performed (data cut-off was February 19, 2019).
Results: A total of 159 patients were enrolled. Stratified efficacy outcomes are shown in the table. The incidence of Grade 3/4 adverse events was similar across lines of therapy.
Number of prior lines of therapy012≥3Total(n=35)(n=48)(n=34)(n=42)(N=159)ORR, % (95% CI)91 (76, 98)70 (54, 82)73 (54, 87)85 (70, 94)79 (72, 85)DoRNENENE35.235.2(19.8, NE)(15.0, NE)(7.6, NE)(22.8, NE)(22.8, NE)1.9+, 37.1+1.6+, 40.2+1.9+, 44.2+1.9+, 38.2+1.6+, 44.2+PFS25.8NENE28.328.3(15.2, NE)(9.9, NE)(7.0, NE)(16.6, NE)(22.1, NE)0.03+, 38.8+0.03+, 42.1+0.03+, 45.2+0.03+, 40.0+0.03+, 45.2+OSNENE36.544.444.4(NE, NE)(33.4, NE)(36.5, NE)(NE, NE)(36.5, NE)0.03+, 39.9+0.5+, 43.1+0.3+, 47.2+1.0+, 44.40.03+, 47.2+ECOG performance status0123Total(n=76)(n=61)(n=19)(n=3)(N=159)ORR, % (95% CI)91 (81, 96)69 (56, 81)71 (44, 90)33 (1, 91)79 (72, 85)DoR35.226.3NENE35.2(22.8, NE)(19.8, NE)(7.2, NE)(22.8, NE)1.8+, 40.2+1.6+, 44.2+1.9+, 29.5+1.6+, 44.2+PFS36.825.8NENE28.3(24.6, NE)(9.0, NE)(2.7, NE)(1.1, NE)(22.1, NE)0.03+, 42.1+0.03+, 45.2+0.03+, 30.4+0.03+, 1.7+0.03+, 45.2+All data values show median (95% CI) and range in months, unless otherwise stated. CI, confidence interval; DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; NE, not estimable; ORR, objective response rate; OS, overall survival; PFS, progression-free survival.
Conclusion: While response rates were highest in patients who were treatment-naïve or with an ECOG performance status of 0, larotrectinib benefited patients across varying degrees of pre-treatment or performance status.
Citation Format: Alexander Drilon, Cornelis M. van Tilburg, Anna F. Farago, Shivaani Kummar, Jordan Berlin, Catherine M. Albert, Ray McDermott, Ulrik N. Lassen, John A. Reeves, Nicoletta Brega, Barrett H. Childs, Theodore W. Laetsch, David S. Hong. Larotrectinib in TRK fusion cancer patients: Outcomes by prior therapy and performance status [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT199.