METASTATIC STS

Rhabdomyosarcoma is a very aggressive tumour with a strong tendency to metastasize. Outcome in patients with localised disease is generally good, but outcome for patients with metastatic RMS remains poor with 3-year overall survival of 34-56%. The single-arm EpSSG MTS 2008 study was introduced as an amendment to RMS 2005.

MTS 2008 was an academic, international, prospective study (NCT00379457) involving 74 hospitals across 11 countries. Patients < 21 years with a histological diagnosis of RMS with distant metastatic disease, < 8 weeks between diagnostic surgery/biopsy and start of chemotherapy, who had received no prior chemotherapy or radiotherapy were eligible. In MTS 2008, patients with
metastatic RMS received 4 cycles of ifosfamide, vincristine, actinomycin D (IVA) plus doxorubicin, 5 cycles of IVA and 12 cycles of maintenance
chemotherapy (low-dose cyclophosphamide and vinorelbine).

Between October 2010 and December 2016 MTS 2008 included 270 patients (median age 9.6 years, range 0.07-20.8). With a median follow-up of 50.3 months, 3-year event free survival (EFS) and overall survival (OS) were 34.9% (95% CI 29.1-40.8%) and 47.9% (95%CI 41.6-53.9%) respectively.

This is an apparent improvement of outcome compared to historical cohorts. However, due to the design of this single arm study it is not possible to differentiate if this is attributable to the addition of doxorubicin or maintenance chemotherapy, or may be
explained by more consistent application of local therapy or improvements in imaging and supportive care, or any combinations of these.

Outcome for metastatic patients with adverse prognostic factors remains poor. The MTS 2008 IVADo backbone followed by a year’s maintenance is the standard backbone in the current FaR-RMS study.