RMS13: A Phase II Trial Using Risk-Adapted Proton Beam Radiation and Surgery With Addition of Antiangiogenic Maintenance Chemotherapy in Intermediate-Risk Rhabdomyosarcoma
Jessica Gartrell, Tushar Patni, Yimei Li, Daniel J. Indelicato, Sara M. Federico, Andrew M. Davidoff, Sara Helmig, Elizabeth Stewart, Christopher L. Tinkle, John T. Lucas, Mary E. McCarville, Eric Sandler, Karen Albritton, Chia-ho Hua, Alberto S. Pappo, Matthew J. KrasinPURPOSE
Outcomes for intermediate-risk (IR) rhabdomyosarcoma (RMS) have remained unchanged for decades. More active chemotherapy regimens, improvements in local control, and the role of maintenance therapy (MTC) remain critical therapeutic questions. RMS13 assessed the safety and efficacy of a risk-adapted local therapy paradigm incorporating proton radiotherapy (RT) and novel MTC comprising sorafenib, bevacizumab, and oral cyclophosphamide (CBvSor) with a vincristine, dactinomycin, and cyclophosphamide (VAC) chemotherapy backbone.
PATIENTS AND METHODS
We report outcomes for patients with IR RMS enrolled on a multicenter phase II trial evaluating risk-adapted local therapy and MTC. Patients received 12 cycles of VAC followed by four to six cycles of CBvSor in MTC-eligible patients. Tumor status at RT initiation determined RT dose. Five-year event-free survival (EFS), overall survival (OS), disease-free survival (DFS), and local failure (LF) are reported.
RESULTS
Forty-five patients enrolled, of whom 35 were eligible for MTC at study entry. Twenty-three patients completed at least four cycles of MTC; however, only 18 of 24 completed treatment with all three agents. Five-year EFS and OS were 68.8% (95% CI, 0.57 to 0.84) and 75.2% (95% CI, 0.63 to 0.89), respectively. Among those receiving ≥3 MTC cycles (n = 24), 5-year DFS was 70.8% (95% CI, 0.55 to 0.92). In patients meeting European Pediatric Soft Tissue Sarcoma Group RMS2005 high-risk criteria, DFS was 82.4%. No LF occurred after margin-negative surgery; LF was 4.8% for all patients receiving local control. Five of six patients with fusion-positive N1 disease recurred. The trial closed early due to a prespecified stopping rule, with MTC completion <75%.
CONCLUSION
Risk-adapted radiation therapy yielded excellent local control in IR RMS. Fusion-positive nodal disease carries a significant negative prognostic value. When ≥3 cycles of CBvSor were administered, improvement in DFS was observed, consistent with other MTC-based studies.