KEY TAKEAWAYS
- Two clinical trials, phase 1 (NCT02122913), and phase 2 NAVIGATE (NCT02576431) were conducted to assess larotrectinib’s success rate in treating TRK fusion lung cancer.
- The study analyzed pts treated with larotrectinib following local testing to determine NTRK gene fusions.
- The study reported the effectiveness and safety of larotrectinib therapy in pts with TRK fusion lung cancer with ctDNA analysis.
Two clinical trials analyzed patients (pts) treated with larotrectinib following local testing to determine neurotrophic tyrosine receptor kinase (NTRK) gene fusions. The administration of larotrectinib at 100 mg twice daily was evaluated by an independent review committee (IRC) per RECIST v1.1. Guardant 360 and GuardantOMNI were used to analyze circulating tumor DNA (ctDNA).
As of July 20, 2021, the study included 26 pts (12 pts with CNS metastases). Out of the 23 pts (10 pts with CNS metastases) evaluated per IRC, the ORR was impressive at 83%, with a 95% confidence interval of 61-95, including two complete responses, 17 partial responses, and 4 stable diseases. The median duration of response (DoR) had yet to be reached, with a 95% confidence interval of 9.5-NE, with a 12-month DoR rate of 72%.
The median progression-free survival was not yet reached, with a 95% confidence interval of 9.9-NE. The median overall survival was calculated to be 40.7 months, with a 95% confidence interval of 19.4-NE. Most of the adverse events associated with the treatment were of Grade 1-2. The ctDNA data showed that 6 out of the 14 pts had NTRK gene fusions at the start of the treatment. Analysis of co-occurring mutations at baseline revealed that 3 pts with NSCLC positive for mutations had previously failed anti-EGFR therapy. By the time of the data cut-off, six pts had experienced progression, with ctDNA data available for 5. Acquired mutations were detected in 3 pts.
Larotrectinib has shown extended survival rates, long-lasting responses, and an exceptional safety profile. It is effective for pts with the NTRK gene fusion, including those without treatment for NSCLC or those who have undergone previous EGFR inhibitor therapy. ctDNA next-generation sequencing technology has made detecting NTRK gene fusions and resistance mutations possible.
Clinical Trials: https://classic.clinicaltrials.gov/ct2/show/NCT02122913
https://classic.clinicaltrials.gov/ct2/show/NCT02576431
Hoejgaard, M., Drilon, A., Lin, J.J., Kummar, S., Tan, D.S.W., Patel, J., Leyvraz, S., Moreno Garcia, V., Rosen, L.S., Solomon, B., Yachnin, J., Liu, Y., Dai, M., Norenberg, R., Burcoveanu, D., Yun, L., Beckmann, G., Mussi, C.E., Shen, L. Journal of Thoracic Oncology (2023).
