Evaluating Strategies for Treating Pediatric Metastatic Rhabdomyosarcoma

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In a report in the Journal of Clinical Oncology, Schoot et al provided findings from the European Paediatric Soft Tissue Sarcoma Study Group MTS 2008 and pooled findings of MTS 2008 with those of the concurrent BERNIE study, both of which evaluated strategies for the treatment of pediatric metastatic rhabdomyosarcoma.

Study Details

The MTS 2008 study enrolled 270 evaluable patients (median age = 9.6 years, range = 0.1–20.8 years) between October 2010 and December 2016 and tested the addition of dose-intense doxorubicin to standard chemotherapy, as well as the addition of maintenance therapy to induction treatment. Patients received 4 cycles of ifosfamide, vincristine, and actinomycin D (IVA) plus doxorubicin, 5 cycles of IVA, and 12 cycles of maintenance chemotherapy with low-dose cyclophosphamide and vinorelbine.

The BERNIE trial concurrently enrolled 102 evaluable patients aged 1 to 17 years who received the same chemotherapy regimens and were randomly assigned to receive (n = 50) or not receive bevacizumab as part of both induction and maintenance therapy; initial findings in the BERNIE trial were previously reported.

In both studies, local therapy (surgery/radiotherapy) was given to the primary tumor and all metastatic sites when feasible.

Key Findings

In the MTS 2008 study, with a median follow-up of 50.3 months, 3-year event-free survival was 34.9% (95% confidence interval [CI] = 29.1%–40.8%) and 3-year overall survival was 47.9% (95% CI = 41.6%–53.9%).

In an updated analysis of the BERNIE trial, with a median follow-up of 71.8 months, 3-year event-free survival was 37.0% (95% CI = 26.2%–47.8%) and 3-year overall survival was 53.1% (95% CI = 42.4%–62.6%). Overall survival did not differ between the bevacizumab and non-bevacizumab groups.

In the pooled analyses of 372 patients from the MTS 2008 and BERNIE trials, with a median follow-up of 55.2 months, 3-year event-free survival was 35.5% (95% CI = 30.4%–40.6%), and 3-year overall survival was 49.3% (95% CI = 43.9%–54.5%).

Among patients in the pooled analysis with known Oberlin risk factor status, 147 had two or fewer Oberlin risk factors and 118 had three or more risk factors. For those with two or fewer risk factors vs those with three or more, 3-year event-free survival was 46.1% vs 12.5% (P < .0001) and 3-year overall survival was 60.0% vs 26.0% (P < .0001).

The investigators wrote, “Induction chemotherapy and maintenance appeared tolerable; however, about two-thirds of patients needed dose adjustments during maintenance.”

They concluded, “Outcome remains poor for patients with metastatic rhabdomyosarcoma and multiple Oberlin risk factors. Because of the design of the studies, it was not possible to determine whether the intensive induction regimen and/or the addition of maintenance treatment resulted in apparent improvement of outcome compared with historical cohorts. Further studies with novel treatment approaches are urgently needed to improve outcome[s] for the group of patients with adverse prognostic factors.”

Reineke A. Schoot, MD, PhD, of Princess Máxima Center for Pediatric Oncology, Utrecht, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Fondazione Città della Speranza, National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust, and Institute of Cancer Research, London. For full disclosures of the study authors, visit

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