136P Efficacy and safety of larotrectinib (laro) as first-line treatment for paediatric (paed) patients (pts) with TRK fusion cancer

Laro is the first-in-class, highly selective, central nervous system (CNS)-active TRK inhibitor approved for tumour-agnostic use in pts with TRK fusion cancer based on a robust and durable overall response rate (ORR) in both adult and paed pts with various tumour types. Here, we report data on paed pts with TRK fusion cancer treated in the first line. Pts with treatment-naïve non-primary CNS TRK fusion cancer were included. Responses were independent review committee (IRC)-assessed (RECIST v1.1). Pts were permitted to stop laro in the absence of on-treatment progression (wait-and-see). As of July 2022, 37 paed pts were eligible for efficacy analyses by IRC. There were 5 tumour types: infantile fibrosarcoma (n=18; 49%), soft tissue sarcoma (n=14; 38%), congenital mesoblastic nephroma (n=2; 5%), thyroid cancer (n=2; 5%) and breast cancer (n=1; 3%). Median age was 2.1 years (range 0–17). NTRK gene fusions were identified by NGS, FISH and RT-PCR in 24, 7 and 6 pts, respectively. ORR was 89% (95% CI 75–97); best overall responses were 26 (70%) complete response (CR; including 5 pathologic CR), 7 (19%) partial response, 3 (8%) stable disease and 1 (3%) not evaluable. Median time to first response was 1.8 months. Medians for duration of response, progression-free survival and overall survival (OS) were 38.4 months (95% CI 23.4–not estimable NE), 40.2 months (95% CI 25.5–NE) and not reached, at median follow-ups of 28.6, 30.3 and 37.8 months, respectively. The 48-month OS rate was 95% (95% CI 87–100). Treatment duration was 1–64+ months (median 31.2 months). At data cut-off, 22 (59%) pts had participated in wait-and-see. Treatment-related adverse events (TRAEs) were mainly Grade 1/2. Grade 3/4 TRAEs occurred in 15 (41%) pts; 2 pts discontinued due to a TRAE (malaise and hypoventilation occurred in one pt each). Laro demonstrated rapid and durable responses, extended survival and had a favourable safety profile in paed pts without prior systemic therapy. This supports the use of laro in a first-line setting and the wider adoption of next-generation sequencing panels that include NTRK gene fusions to identify paed pts who may benefit from targeted treatment.