The following article features coverage from the European Society for Medical Oncology (ESMO) 2018 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Larotrectinib, a selective TRK inhibitor, continues to demonstrate efficacy against TRK-fusion cancers, regardless of patient age and tumor type, according to results from an analysis of 3 clinical trials presented at the ESMO 2018 Congress in Munich, Germany.1

Larotrectinib targets the protein products of NTRK1/2/3 gene fusions and previously demonstrated an overall response rate (ORR) of 75% among 55 consecutive adult and pediatric patients with TRK-fusion cancers. This analysis provides updated results for those 55 patients and an additional 35 patients enrolled in larotrectinib clinical trials as of February 19, 2018.

TRK fusions were detected by molecular profiling of patients from 3 larotrectinib clinical trials. Treatment was administered until disease progression, withdrawal, or unacceptable toxicity.

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Among the initial 55 patients and during a median 12.9 months of follow-up, the median duration of response (DoR) and progression-free survival (PFS) had not yet been reached. In this cohort, responses were ongoing in 69% of patients, 58% were progression-free, and 90% were sill alive at 1 year. 

There were an additional 44 adult and pediatric patients enrolled after the primary analysis set (age range, 0.1-78 years) with various cancer types, including malignancies of the lung, colon, thyroid, salivary gland, as well as melanoma, sarcoma, congenital mesoblastic nephroma, and gastrointestinal stromal tumors. 

Among the 35 evaluable patients in this cohort, the ORR was 74%, which included 5 complete and 21 partial responses, 6 stable disease, 2 with progressive disease, and 1 who was undetermined. The median DoR was not reached during a median follow-up of 5.5 months, but 88% of response were ongoing at 6 months.

Most adverse events (AEs) were grade 1 in severity, with the most common including dizziness, elevated liver enzymes, fatigue, nausea, and constipation. Grade 3/4 AEs related to larotrectinib treatment occurred in fewer than 5% of patients.

The authors concluded that, “Larotrectinib is an effective age- and tumor-agnostic treatment for TRK-fusion cancer with a positive safety profile.” They noted that these results suggest that “screening patients for NTRK gene fusions in solid [tumors] and brain tumors should be actively considered.”

Read more of Cancer Therapy Advisor‘s coverage of the ESMO 2018 meeting by visiting the conference page.

Reference

  1. Lassen UN, Albert CM, Kummar S, et al. Larotrectinib efficacy and safety in TRK fusion cancer: an expanded clinical dataset showing consistency in an age and tumor agnostic approach. Presented at: the ESMO 2018 Congress; Munich, Germany: October 19-23, 2018. Abstract 409O.