Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2024 May;9(5):103006.
doi: 10.1016/j.esmoop.2024.103006. Epub 2024 Apr 23.

Therapeutic benefit of larotrectinib over the historical standard of care in patients with locally advanced or metastatic infantile fibrosarcoma (EPI VITRAKVI study)

D Orbach  1 , M Carton  2 , S K Khadir  3 , M Feuilly  4 , M Kurtinecz  5 , D Phil  5 , C Vokuhl  6 , E Koscielniak  7 , G Pierron  8 , L Lemelle  9 , M Sparber-Sauer  7
Affiliations
Observational Study

Therapeutic benefit of larotrectinib over the historical standard of care in patients with locally advanced or metastatic infantile fibrosarcoma (EPI VITRAKVI study)

D Orbach et al. ESMO Open. 2024 May.

Abstract

Background: Patients with infantile fibrosarcoma (IFS) have shown strong and long-lasting responses to larotrectinib, a tropomyosin receptor kinase inhibitor (TRKi), in single-arm clinical trials. Conventional chemotherapy has also shown important efficacy. But, until now, no comparative data exist. This study aims to assess the therapeutic benefit of larotrectinib over the current standard of care (SOC) of chemotherapy in paediatric patients with locally advanced or metastatic IFS.

Patients and methods: EPI VITRAKVI is a retrospective, observational, externally controlled study (NCT05236257). Data of patients aged ≤21 years with locally advanced or metastatic IFS treated with larotrectinib in the phase I/II SCOUT trial (NCT02637687) were compared with those of an external historical control group (data of Institut Curie and Cooperative Weichteilsarkom Studiengruppe) treated with a chemotherapy-based regimen. Between-group differences were assessed after balancing groups using inverse probability of treatment weighting (IPTW).

Results: In total, 93 patients were compared, 51 in the larotrectinib arm and 42 in the external control arm. After therapy, 4 patients (7.8%) in the larotrectinib group had a medical treatment failure event [start of new systemic treatment (2 cases), mutilating surgery (2 cases)] versus 15 (35.7%) in the external control group [start of new systemic treatment (6 cases), mutilating surgery (5 cases), radiation therapy (2 cases), and death (2 cases)]. Larotrectinib was associated with an 80% reduced likelihood of encountering a medical treatment failure event, when compared to the external control group (weighted and stratified hazard ratio 0.20, 95% confidence interval 0.06-0.63, P = 0.0060). These results were confirmed by sensitivity analyses, including exact matching, and subgroup analyses for number of lines of treatment.

Conclusions: Treatment with larotrectinib reduced the need of subsequent therapies compared to SOC with chemotherapy in children with locally advanced or metastatic IFS, regardless of the line of treatment.

Keywords: NTRK; TRK inhibitor; external historical control; infantile fibrosarcoma; larotrectinib.

PubMed Disclaimer

Conflict of interest statement

Disclosure SKK, MF, and MK are Bayer employees. DO had a consultant activity for Bayer and Roche and is an Independent Data Monitoring Committee (IDMC) member for a Lilly product and is a consultant for Novartis Pharma France and Eusapharm. MC had a consultant activity for Bayer. MSS had advisory activity for Bayer, Roche, and Sobi. All other authors have declared no conflicts of interest.

Figures

Figure 1
Figure 1
Kaplan–Meier plot of time to medical treatment failure according to treatment groups. The HR was weighted by stabilized IPTW (adjusted for IRS group classification, age at index, and time from locally advanced/metastatic disease diagnosis to treatment initiation) and stratified by IRS groups. A hazard ratio <1 favours the larotrectinib group. CI, confidence interval; HR, hazard ratio; IPTW, inverse probability of treatment weighting; IRS, Intergroup Rhabdomyosarcoma Study.
Figure 2
Figure 2
Kaplan–Meier plots of the individual components of the composite endpoint, consisting of (A) subsequent systemic treatment, (B) radiation therapy, (C) mutilating surgery, and (D) overall survival. The HR was weighted by stabilized IPTW (adjusted for IRS group classification, age at index, and time from locally advanced/metastatic disease diagnosis to treatment initiation) and stratified by IRS groups. HRs of time to radiation therapy could not be calculated due to the lack of events in the larotrectinib group. CI, confidence interval; HR, hazard ratio; IPTW, inverse probability of treatment weighting; IRS, Intergroup Rhabdomyosarcoma Study.
See this image and copyright information in PMC

References

    1. Orbach D., Brennan B., Paoli A., et al. Conservative strategy in infantile fibrosarcoma is possible: the European paediatric Soft tissue sarcoma Study Group experience. Eur J Cancer. 2016;57:1–9. - PubMed
    1. Parida L., Fernandez-Pineda I., Uffman J.K., et al. Clinical management of infantile fibrosarcoma: a retrospective single-institution review. Pediatr Surg Int. 2013;29(7):703–708. - PMC - PubMed
    1. Orbach D., Rey A., Cecchetto G., et al. Infantile fibrosarcoma: management based on the European experience. J Clin Oncol. 2010;28:318–323. - PubMed
    1. Orbach D., Sparber-Sauer M., Laetsch T., et al. Spotlight on the treatment of infantile fibrosarcoma in the era of neurotrophic tropomyosin receptor kinase inhibitors: international consensus and remaining controversies. Eur J Cancer. 2020;137:183–192. - PubMed
    1. Sparber-Sauer M., Vokuhl C., Seitz G., et al. The impact of local control in the treatment of children with advanced infantile and adult-type fibrosarcoma: experience of the cooperative weichteilsarkom studiengruppe (CWS) J Pediatr Surg. 2020;55(9):1740–1747. - PubMed

Publication types

LinkOut - more resources