Larotrectinib appeared to have durable efficacy and long-term safety in patients with TRK fusion-positive cancer, according to data from an expanded pooled analysis recently reported in the Lancet Oncology.

In a corresponding editorial, Christian Rolfo, MD, PhD, University of Maryland, Baltimore, described the results as “noteworthy” because the accelerated approval of larotrectinib was based only on phase 1 studies examining 55 patients, and the durability of benefit and long-term safety of larotrectinib had not been “fully elucidated.”2

The efficacy analysis included 159 adult and pediatric patients with TRK fusion-positive cancer aged less than 1 month to 84 years who received larotrectinib in 1 of 3 clinical trials: a phase 1 ( identifier: NCT02122913), a phase 1/2 ( identifier: NCT02637687), and a phase 2 ( Identifier: NCT02576431).

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Among the 153 evaluable patients, responses were seen in 121 (79%), which included 24 complete responses (16%). At a median follow-up of 12.9 months (interquartile range [IQR], 5.7–23.1), 23% of patients with a confirmed response had disease progression and responses lasted a median of 35.2 months (95% CI, 22.8–not estimable [NE]).

At a median follow-up of 11.1 months (IQR, 5.5–22.1), the study population had a median progression-free survival (PFS) of 28.3 months (95% CI, 22.1–NE), and a 12-month PFS rate of 67% (95% CI, 58–76). The study population had a median overall survival (OS) of 44.4 months (95% CI, 36.5–NE) and an estimated 12-month OS rate of 88% (95% CI, 83–94).

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A total of 260 who received larotrectinib regardless of TRK fusion status were included in the safety analysis. Grade 3 treatment-emergent adverse events (TEAEs) occurred in 39% of patients, with increased alanine aminotransferase levels (3%), anemia (2%) and decreased neutrophil count (2%) being related to treatment. Grade 4 TEAEs occurred in 7% of patients, which included 1 patient with decreased neutrophil count and 1 patient with increased alanine aminotransferase levels.

The study authors encouraged testing for TRK fusions in the clinic to identify patients who may be eligible for larotrectinib treatment,1 and Dr Rolfo agreed.2

Disclosures: The study funders were Bayer and Loxo Oncology. Some of the authors reported financial relationships with pharmaceutical and/or medical device companies. For a full list of disclosures, please refer to the original studies.


  1. Hong DS, DuBois SG, Kummar S, et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials [published online February 24, 2020]. Lancet Oncol. doi: 10.1016/S1470-2045(19)30856-3
  2. Rolfo C. NTRK gene fusions: a rough diamond ready to sparkle [published online February 24, 2020]. Lancet Oncol. doi: 10.1016/S1470-2045(20)30026-7