62O - Treatment discontinuation outcomes in paediatric patients with TRK fusion sarcomas treated with larotrectinib

Background

NTRK gene fusions are oncogenic drivers in multiple tumour types. Larotrectinib (laro) is the first-in-class, highly selective TRK inhibitor approved for tumour-agnostic use in patients (pts) with TRK fusion cancer. Here, we report outcomes in paediatric pts with TRK fusion sarcomas who electively stopped laro while in response.

Methods

Pts with TRK fusion cancer treated in the SCOUT trial (NCT02637687) were permitted to stop laro in the absence of on-treatment disease progression per investigator (INV) assessment (wait-and-see); pts who stopped laro were followed for progression. Pts who progressed were re-treated with laro and were reassessed by INV per RECIST v1.1. Most pts received laro 100 mg/m² (maximum dose: 100 mg) twice daily. Data cut-off date was 20 July 2023.

Results

At data cut-off, 47 paediatric pts (<18 years old) with TRK fusion sarcomas had stopped laro in the absence of on-treatment progression: 30 (64%) with infantile fibrosarcoma and 17 (36%) with other soft tissue sarcoma. Median age was 1 year (range 0–13). Median time to stopping laro was 15 months (range 3–65). Twenty-one (45%) pts stopped after surgery and 26 (55%) did not have surgery. Twenty-five (53%) pts stopped after achieving complete response (CR; including 10 surgical pts with pathologic CR), 18 (38%) with partial response (PR) and 4 (9%) with stable disease (SD). Sixteen (34%) pts who stopped laro had subsequent progression. Median time from stopping laro to progression in these pts was 3 months (range 1–35). All 16 pts resumed laro after documented progression; 11 had response to re-treatment (5 CR, 6 PR [2 pending confirmation]), 4 had SD and 1 restarted treatment and then had surgery, so response was undefined. All 47 pts were alive at data cut-off. Treatment-related adverse events (TRAEs) were mostly Grade 1/2. Grade 3/4 TRAEs occurred in 16 (34%) pts. No pts discontinued due to a TRAE.

Conclusions

Laro demonstrated robust, durable responses and favourable safety in paediatric pts with TRK fusion sarcomas who had a drug holiday. Stopping treatment is feasible following surgical resection or durable response, with most pts benefitting clinically with laro resumption on disease progression.

Clinical trial identification

NCT02637687.

Editorial acknowledgement

Medical writing assistance was provided by Anastasija Pesevska, PharmD, and editorial assistance was provided by Melissa Ward, BA, both of Scion (a division of Prime, London, UK), supported by Bayer Healthcare Pharmaceuticals.

Legal entity responsible for the study

Bayer HealthCare Pharmaceuticals, Inc.

Funding

Bayer HealthCare Pharmaceuticals, Inc.

Disclosure

L. Mascarenhas: Financial Interests, Institutional, Other, Research funding to previous institution: Amgen, AstraZeneca, Merck, Novartis, Pfizer, Turning Point. D. Orbach: Financial Interests, Institutional, Other, Consultant work (consultancy agreement signed with the institution): French larotrectinib transparency committee; Financial Interests, Institutional, Other, An independent translational research project conducted by him is partially supported by Bayer (investigator supported research): Bayer; Financial Interests, Personal, Other, Consultancy: Bayer Healthcare, EUSA Pharma, Hoffman La Roche, Lilly, Merck, Novartis, Sanofi. N. Federman: Financial Interests, Personal, Other, Honorarium for speaker and ad hoc advisory roles:: Bayer AG, Fennec Pharma, Springworks; Financial Interests, Personal, Research Grant, NCATS ULTR001881: NIH; Financial Interests, Personal, Research Grant, INFR4-13685: California Institute for Regenerative Medicine. S. Dubois: Financial Interests, Personal, Other, Consulting/advisory board roles: Bayer, Jazz, Loxo Oncology; Financial Interests, Personal, Other, Travel expenses: Loxo Oncology, Roche/Genentech, Salarius Pharmaceuticals. A. Pappo: Financial Interests, Personal, Other, Personal fees: Bayer. C.M. Zwaan: Financial Interests, Institutional, Other, Institutional funding: Abbvie, Jazz, Pfizer, Takeda; Financial Interests, Personal, Other, Travel funding: Jazz; Financial Interests, Personal, Other, Consultancy: Incyte, Novartis, Roche, Takeda. D. Burcoveanu, N. Neu, E.A. De La Cuesta: Financial Interests, Personal, Full or part-time Employment: Bayer. T. Laetsch: Financial Interests, Personal, Other, Consulting/advisory boards: Advanced Microbubbles, AI Therapeutics, Bayer, GSK, ITM Oncologics, Jazz Pharmaceuticals; Financial Interests, Personal, Other, Research support: Bayer, Eli Lilly, Exelixis, Pfizer. C. Van Tilburg: Financial Interests, Personal, Advisory Board: Alexion, Bayer, Novartis. All other authors have declared no conflicts of interest.