For patients with infantile fibrosarcoma (IFS), clinical trials have shown pronounced and durable responses to larotrectinib, a TRK kinase inhibitor. The aim of this study was to assess the effectiveness of Larotrectinib over standard of care (SOC) with chemotherapy, by comparing the time to medical treatment failure (next systemic therapy, mutilating surgery, radiation therapy or death due to any cause) between Larotrectinib and SOC.
Retrospective observational externally-controlled phase IV study. Data of patients with locally advanced or metastatic IFS, in the phase I/II ‘SCOUT’ clinical trial treated with Larotrectinib (NCT02637687) were compared with the historical control cohorts (data of Institut Curie-Paris and CWS-Cooperative Weichteilsarkom Studiengruppe) treated with chemotherapy-based regimen.
Mean (SD) age of 93 included patients (n=51 [Larotrectinib] and n=42 [control]) was 1.4 (2.9) years: Larotrectinib 2.0 (3.5); control 0.7 (1.8). Locally advanced IFS rates were 80.4% (Larotrectinib) and 92.9% (control). Median durations of follow-up were 30.9 (Larotrectinib) and 72.9 months (control). Four Larotrectinib patients (7.8%) reported a medical treatment failure event (new systemic treatment [n=2], mutilating surgery [n=2]) versus 15 (35.7%) in control group (new systemic treatment [n=6], mutilating surgery [n=5], radiation therapy [n=2] and death [n=2]). Time to medical treatment failure was significantly longer in the Larotrectinib group (weighted log-rank test: p=0.0161). Weighted Hazard Ratio stratified by IRS group stage was 0.20 (95%CI: 0.06-0.63; p=0.0060), which corresponds to an 80% lower likelihood of experiencing a medical treatment failure in the Larotrectinib group. These results were confirmed by sensitivity analyses, including exact matching and subgroup analysis for number of lines of treatment.
This is the first study to provide comparative data on Larotrectinib versus SOC in IFS patients. Results indicate that treatment with Larotrectinib reduced the morbidity and the need of aggressive local therapies compared to SOC in children with IFS.
NCT05236257.
Bayer Inc.
Bayer Inc.
D. Orbach: Financial Interests, Institutional, Advisory Board, French Larotrectinib Transparency Committee: Bayer; Financial Interests, Institutional, Invited Speaker, Larotrectinib: Bayer; Financial Interests, Institutional, Advisory Board, IDMC for an experimental product: Lilly; Financial Interests, Institutional, Expert Testimony: Roche, Eusapharm; Financial Interests, Institutional, Invited Speaker, An independent translational research project conducted by him is partially supported by Bayer. L. Lemelle, M. Carton, G. Pierron: Financial Interests, Institutional, Funding: Bayer. S.K. Khadir, M. Feuilly, M. Kurtinecz: Financial Interests, Personal, Full or part-time Employment: Bayer. M. Sparber-Sauer: Financial Interests, Institutional, Advisory Board: Bayer, Sobi, Roche. All other authors have declared no conflicts of interest.