(P 396) LONG-TERM FOLLOW-UP EFFICACY AND SAFETY OF LAROTRECTINIB IN ADULT PATIENTS WITH TRK FUSION SARCOMAS

Objective: NTRK gene fusions are oncogenic drivers in multiple tumor types, including sarcoma. Larotrectinib is the first-in-class, highly selective TRK inhibitor, approved for tumor-agnostic use in patients (pts) with TRK fusion cancer, based on a robust and durable objective response rate in both adult and pediatric pts with various cancers. Here, we report updated long-term efficacy and safety of larotrectinib in adult pts with TRK fusion sarcomas.

Methods: Adult pts (≥18 years old) with TRK fusion sarcomas treated with larotrectinib were identified from 3 clinical trials (NCT02122913, NCT02576431 [NAVIGATE], NCT02637687 [SCOUT]). Most pts received larotrectinib 100 mg twice daily. Responses were assessed by an independent review committee (IRC) per Response Evaluation Criteria in Solid Tumours v1.1. The data cutoff date was July 20, 2023.

Results: At data cutoff, 38 pts were eligible for efficacy assessment by IRC. Median age was 43 years (range 19–70). Thirty-one (82%) pts had soft tissue sarcomas, 7 (18%) had other sarcoma types (Table 1). NTRK gene fusions were identified by next-generation sequencing (NGS) and fluorescence in situ hybridization in 37 (97%) and 1 (3%) pt, respectively. Fifteen (39%) pts were treatment naïve, whereas 12 (32%) and 11 (29%) pts had received 1 or ≥2 prior systemic therapies, respectively.

The overall response rate was 55% (95% confidence interval [CI] 38–71): 9 (24%) pts had complete responses (CR; including 1 pathological CR), 12 (32%) had partial responses, 9 (24%) had stable disease, and 7 (18%) had progressive disease; response in 1 pt (3%) was not evaluable (Table 2). Median time to response was 1.8 months (range 1.0–22.9). Median duration of response (DoR) was 55 months (95% CI 17–not estimable [NE]); median follow-up (f/u) was 39 months. Median progression-free survival (PFS) was 19 months (95% CI 6–NE); median f/u was 41 months. Median overall survival (OS) was not reached (95% CI 39–NE); median f/u was 46 months (Table 2). The 4-year rates for DoR, PFS, and OS were 58% (95% CI 35–81), 42% (95% CI 25–59), and 60% (95% CI 42–78), respectively. Treatment duration was 0–72+ months. Treatment-related adverse events (TRAEs) were mostly Grade 1/2, with only 1 Grade 3 TRAE reported (increased weight). There were 2 Grade 5 adverse events (both due to disease progression), neither of which were considered related to larotrectinib. There were no discontinuations due to TRAEs.

Conclusion: In this updated analysis, larotrectinib continues to demonstrate a rapid and durable response, extended survival benefit, and a favorable safety profile in adult pts with TRK fusion sarcomas. These results support the wider adoption of NGS panels that include NTRK gene fusions to identify pts who may benefit from treatment.