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Discussion led by
- Binghe Xu
- Binghe Xu
Skull base tumours
- Prathamesh Pai
- Prathamesh Pai
Discussion led by
- Lisa F. Licitra
- Lisa F. Licitra
What is the optimal first-line chemotherapy for advanced soft-tissue sarcoma?
- Axel Le Cesne
- Axel Le Cesne
Discussion led by
- Herbert H. Loong
- Herbert H. Loong
Introduction
- Tetsuya Mitsudomi
- Tetsuya Mitsudomi
1st line immunotherapy options for patients without an oncogene driver
- Ross A. Soo
- Ross A. Soo
What is the biological rationale for combining chemotherapy with immune checkpoints inhibitors?
- Marina C. Garassino
- Marina C. Garassino
Are ICPs better as single agent, doublet ICPs or combined with Chemo +/- anti-angiogenics?
- Solange Peters
- Solange Peters
What’s new in the guidelines for immune therapy of metastatic NSCLC?
- David Planchard
- David Planchard
Conclusions
- Tetsuya Mitsudomi
- Tetsuya Mitsudomi
69O - Larotrectinib efficacy and safety in TRK fusion cancer: an expanded clinical dataset showing consistency in an age and tumor agnostic approach
- Daniel Shao Weng Tan
- Daniel Shao Weng Tan
- Ulrik N. Lassen
- Catherine M. Albert
- Shivaani Kummar
- Cornelis Van Tilburg
- Steven G. Dubois
- Birgit Geoerger
- Leo Mascarenhas
- Noah Federman
- Atrayee Basu-Mallick
- François Doz
- Jordan D. Berlin
- Do-Youn Oh
- Stefan Bielack
- Raymond McDermott
- Scott Cruickshank
- Nora C. Ku
- Michael C. Cox
- Alexander Drilon
- David S. Hong
Abstract
Background
TRK fusion cancer results from gene fusions involving NTRK1, NTRK2 or NTRK3. Larotrectinib, the first selective TRK inhibitor, has demonstrated an overall response rate (ORR) of 75% with a favorable safety profile in the first 55 consecutively enrolled adult and pediatric patients with TRK fusion cancer (Drilon et al., NEJM 2018). Here, we report the clinical activity of larotrectinib in an additional 35 TRK fusion patients and provide updated follow-up of the primary analysis set (PAS) of 55 patients as of 19th Feb 2018.
Methods
Patients with TRK fusion cancer detected by molecular profiling from 3 larotrectinib clinical trials (NCT02122913, NCT02637687, and NCT02576431) were eligible. Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Disease status was assessed using RECIST version 1.1.
Results
As of Feb 2018, by independent review, 6 PRs in the PAS deepened to CRs. The median DoR and progression-free survival in the PAS had still not been reached, with 12.9 months median follow-up. At 1 year, 69% of responses were ongoing, 58% of patients remained progression-free and 90% of patients were alive. An additional 19 children and 25 adults (age range, 0.1-78 years) with TRK fusion cancer were enrolled after the PAS, and included cancers of the salivary gland, thyroid, lung, colon, melanoma, sarcoma, GIST and congenital mesoblastic nephroma. In 35 evaluable patients, the ORR by investigator assessment was 74% (5 CR, 21 PR, 6 SD, 2 PD, 1 not determined). In these patients, with median follow-up of 5.5 months, median DoR had not yet been reached, and 88% of responses were ongoing at 6 months, consistent with the PAS. Adverse events (AEs) were predominantly grade 1, with dizziness, increased AST/ALT, fatigue, nausea and constipation the most common AEs reported in ≥ 10% of patients. No AE of grade 3 or 4 related to larotrectinib occurred in more than 5% of patients.
Conclusions
TRK fusion cancer is detected in a broad range of tumor types. Larotrectinib is an effective tumor-agnostic treatment for TRK fusion cancer with a favorable safety profile. Screening patients for NTRK gene fusions in solid tumors should be actively considered.
Clinical trial identification
NCT02122913; NCT02637687; NCT02576431.
Legal entity responsible for the study
Loxo Oncology Inc and Bayer AG.
Funding
Loxo Oncology Inc; Bayer AG.
Disclosure
S. Cruickshank, N.C. Ku, M.C. Cox: Employment: Loxo Oncology Inc. All other authors have declared no conflicts of interest.