Larotrectinib versus historical standard of care in patients with infantile fibrosarcoma: protocol of EPI-VITRAKVI

Figures & data

Table 1. Selection criteria of data sources for the external historical control arm.

Inclusion criteria

Exclusion criteria

• Cohorts with prospective enrollment • Cohorts with prospective and retrospective data collection from 2000 to 2021 • Cohorts containing at least clinical data allowing for an assessment of the efficacy of treatment and main prognostic factors: ○ Diagnosis and stage of the disease (locally advanced or metastatic) ○ Type of treatments (chemotherapy, radiotherapy, surgery: mutilating yes/no) and date of the initiation or of the procedure ○ Death and date ○ Localization of the tumor (axis vs limb) ○ Size of the tumor (<5 vs >5 cm)

• Databases not containing patients with locally advanced or metastatic infantile fibrosarcoma • Medico-administrative databases or absence of data allowing the assessment of the efficacy of the treatment and main prognostic factors, or high rate of missing data (>10% on outcome and >25% on covariates) • Cohorts with retrospective enrollment and case reports • Cohorts with prospective enrollment for which all patients were included before 2000

Figure 1. Overview of the study arms.

CWS: Cooperative Weichteilsarkom Studiengruppe; SFCE: Société Française de lutte contre les Cancers et les leucémies de l’Enfant et de l’adolescent; SoTiSaR: Soft Tissue Sarcoma Registry.

Table 2. Patient selection criteria.

Inclusion criteria

Exclusion criteria

• Age ≤21 years old • Locally advanced or metastatic IFS (also including patients with advanced or metastatic CMN since histopathological characteristics of these tumors are very close to those of IFS) • Available information on clinical, radiological characteristics of their tumor, therapies administered and outcomes • Patients receiving larotrectinib in the SCOUT trial, or at least one chemotherapy-based regimen in the external historical control cohorts • No opposition from the patients and/or representatives for data use

• Patients treated with TRKi in the external historical control cohorts • Patients with documented absence of NTRK gene fusion • Patients participating in an investigational program (other than SCOUT) with interventions outside of routine clinical practice

CMN: Congenital mesoblastic nephroma; IFS: Infantile fibrosarcoma; TRKi: Tropomyosin receptor kinase inhibitor.

Table 3. Study end points.

Primary end point	Time to medical treatment failure: defined as the time (months) from the start of treatment to the date of the following events, whichever comes first: subsequent systemic line of treatment, radiation therapy, mutilating surgery or death due to any cause. Conservative surgery (in other words, surgical resection other than amputation and other mutilating surgeries) will not be considered as an event
Secondary end points	• Time to subsequent systemic treatment: defined as the time from start of treatment till the start date of a post-treatment systemic anticancer therapy, if any • Time to mutilating surgery including limb amputation: defined as the time from start of treatment till the start date of mutilating surgery (including limb amputation), if any • Time to radiation therapy: defined as the time from start of treatment till the start date of radiation therapy, if any • Time to complete surgical resection: defined as the time from start of treatment till the start date of a complete surgical resection (excluding amputation and other mutilating surgeries) • Overall survival: defined as the time from the start of treatment to the date of death due to any cause • Incidence of patients with treatment discontinuation due to treatment emergent adverse events (regardless of relationship to treatment)
Exploratory end points	• Progression-free survival: defined as the time from the start of treatment to the date of first observed disease progression (radiological or clinical, whichever is earlier; assessed by the treating physician in the external historical control cohort(s)) or death due to any cause, if death occurs before progression is documented • Overall response rate: defined as the proportion of patients with a best overall response of CR or PR, as assessed by investigators • Disease control rate: defined as the proportion of patients with a best overall response of CR, PR or SD

The index date (start of treatment) will be defined as either the start date of larotrectinib treatment (for patients in the SCOUT study, regardless of line of therapy) or start date of chemotherapy (first line) for the external historical controls.

CR: Complete response; PR: Partial response; SD: Stable disease.