For the vast majority of patients with rhabdomyosarcoma, a rare soft-tissue sarcoma occurring more commonly in children, standard therapy comprising of surgery, radiation, and high-dose chemotherapy leads to long-term survival and potential cure. However, for high-risk patients or those who progress on first-line therapy, outcomes are poor. With a cure rate of only 20% to 30%, strategies at improving outcomes for these high-risk patients are needed.
During the plenary session at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, Gianni Bisogno, MD, PhD (University Hospital Padova, Padova, Italy), presented results from a phase III trial that investigates low-dose chemotherapy as maintenance therapy for children with rhabdomyosarcoma at high-risk of recurrence (due to tumor location) following standard therapy. Following completion of 6 to 8 months of induction therapy, patients aged 6 months to 21 years (N = 371) with no radiological evidence of tumor, either stopped therapy or received 6 month of maintenance therapy with low-dose vinorelbine (25 mg/m2 intravenous on days 1, 8, and 15 of each cycle) and cyclophosphamide (25 mg/m2 orally daily).
Maintenance chemotherapy resulted in significant improvements in outcomes compared to stopping therapy. Five years post-diagnosis, the disease-free survival (DFS) rate was 77.6% for patients receiving maintenance therapy, compared to 69.8% in patients stopping therapy (HR 0.68, P = .0613). Similar improvements were seen in 5-year overall survival (OS: 86.5% vs 73.7%; HR 0.52, P = .0111).
The most common grade 3/4 adverse event (AE) observed in patients receiving maintenance chemotherapy were low blood cell counts. Febrile neutropenia occurred in 25%. Importantly, treatment-associated AEs were generally much lower in comparison to what is typically seen with standard-dose chemotherapy, including a lower rate of infections (29.4% vs 56%). There were no cardiac, hepatic, or renal toxicities.
Dr Bisogno concluded that maintenance therapy with low-dose chemotherapy is an effective and well-tolerated treatment for children with rhabdomyosarcoma, and that this treatment should be considered the new standard of care, particularly for high-risk patients. In the discussion, Douglas Hawkins, MD (Fred Hutchinson Cancer Research Center, Seattle, Washington, United States), agreed that maintenance chemotherapy can now be considered standard for high-risk patients with rhabdomyosarcoma, particularly given the low toxicity of this combination, but indicated that studies investigating the efficacy of this approach in other patients, including those with distant metastases, will be needed.