OBJECTIVES:

For patients with tumors that harbor NTRK gene fusions, TRK inhibitors provide an effective treatment option with a durable response rate as demonstrated in several single arm trials. The effectiveness data of non-TRKi in these patients, however, is very limited. This systematic literature review evaluated the clinical effectiveness of non-TRKi therapies in patients with NTRK fusion cancer.

METHODS:

MEDLINE and Embase were searched via Ovid.com from database inception to October 26, 2021. Abstracts from recent conferences were also searched. Search terms included NTRK and outcome-specific terms (survival, progression, response). Literature screening was performed by a single reviewer at the title/abstract phase, with a second, independent review of excluded articles at the full-text review phase.

RESULTS:

A total of 2,390 citations were screened, and 10 studies (454 patients) met the inclusion criteria. Nine studies investigated patient characteristics, prognostic factors, and patient outcomes broadly, and 1 study evaluated the comparative effectiveness of treatments. Tumor types varied considerably; the most common were lung, colorectal, breast, and sarcoma. Most studies did not provide details of treatments administered. Median overall survival ranged from 10.1 to 18 months, with varying index date. Progression-free survival ranged from 2.1 to 13.6 months, except one study reporting 196.5 months with >15 years of follow-up. In a study of locally advanced or metastatic cancer, overall response rate (ORR) ranged from 7.7% to 15.8%. In another study that also included localized, stage I-II cancers, the ORR range was 11.1% to 62.5%.

CONCLUSIONS:

Clinical effectiveness data for NTRK fusion cancers treated with non-TRKi therapy is sparse. Small sample size, heterogeneity in patient populations, different study designs/analyses, and lack of details of treatments impede meaningful synthesis and generalizability. Further study of effectiveness of non-TRKi therapies will help provide a benchmark for evaluation of the clinical value of TRKi.