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A Tale of Two TRK Inhibitors: Comparison of Entrectinib and Larotrectinib

By: Lauren Harrison, MS
Posted: Friday, May 27, 2022

A group of researchers utilized a matching-adjusted indirect comparison to evaluate two tyrosine receptor kinase (TRK) inhibitors: larotrectinib and entrectinib. In this study, larotrectinib proved to be more efficacious in prolonging patient survival than entrectinib, although both drugs have similar safety profiles. Ulrik Lassen, MD, PhD, of Rigshospitalet, Copenhagen, and his colleagues published their comparative findings in Cancers.

“Based on treatment guidelines, health-care stakeholders have only one opportunity to decide which TRK inhibitor to select for patients. The results of this analysis can help physicians decide between available treatment options for TRK fusion-positive solid cancer,” stated the authors.

This study utilized data from three clinical trials for larotrectinib and three clinical trials for entrectinib. For this secondary analysis, the authors focused on data from 331 patients. Patients were matched on available baseline characteristics, such as sex, age, race, tumor type (thyroid, sarcoma, salivary, lung, gastrointestinal tumors), metastatic disease, NTRK fusion type, and prior therapy for metastatic disease.

Prior to matching, the median overall survival for larotrectinib was not reached, whereas the median overall survival for entrectinib was 23.9 months. After matching, larotrectinib had a longer overall survival than entrectinib, with a hazard ratio of 0.43 (P < .05). In addition, progression-free survival with larotrectinib was numerically longer than with entrectinib after matching (hazard ratio = 0.66, P = .07). The objective response rate was higher for patients receiving larotrectinib (67.3%), resulting in a risk difference of 3.8% (P = .63). The median duration of response was significantly longer with larotrectinib compared with entrectinib as well (hazard ratio = 0.49, P < .05).

When safety outcomes between the two treatments were compared, larotrectinib had numerically lower rates of treatment-related adverse events (risk difference = –4.6%, P = .27). However, after matching, the results were more similar between the two treatment groups (serious adverse event risk difference = –3.7%, P = .40).

Disclosure: For a full list of authors’ disclosures, visit

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