In the phase III RMS 2005 trial reported by Gianni Bisogno, MD, and colleagues in The Lancet Oncology, maintenance vinorelbine and low-dose continuous cyclophosphamide was associated with nonsignificant improvement in disease-free survival and significantly improved overall survival vs no further treatment in patients with high-risk rhabdomyosarcoma in remission after standard therapy.
Gianni Bisogno, MD
Study Details
In the open-label study, 371 patients from 102 hospitals in 14 countries who achieved remission after standard therapy (nine cycles of ifosfamide, vincristine, dactinomycin with or without doxorubicin, and surgery or radiotherapy, or both) were randomly assigned between April 2006 and December 2016 to receive maintenance chemotherapy (n = 185) or to stop treatment (n = 186). Patients were aged 6 months to 21 years old, and had rhabdomyosarcoma considered to be at high risk of relapse. Maintenance chemotherapy consisted of six 4-week cycles of vinorelbine 25 mg/m2 on days 1, 8, and 15, and daily oral cyclophosphamide 25 mg/m2 on days 1 to 28 of each cycle.
The primary outcome was disease-free survival in the intention-to-treat population.
Disease-Free and Overall Survival
Median follow-up was 60.3 months. Disease-free survival at 5 years was 77.6% in the maintenance chemotherapy group vs 69.8% in the control group (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.45–1.02, P = .061). Overall survival at 5 years was 86.5% vs 73.7% (HR = 0.52, P = .0097).
In per-protocol analysis in 367 patients, 5-year disease-free survival was 77.8% in the maintenance chemotherapy group vs 69.6% in the control group (HR = 0.67, 95% CI = 0.44–1.01, P = .053) and 5-year overall survival was 86.3% vs 73.5% (HR = 0.53, P = .011).
KEY POINTS
- Improvement in disease-free survival with maintenance chemotherapy approached statistical significance.
- Maintenance chemotherapy was associated with better overall survival.
Toxicity During Maintenance Therapy
Among the patients who received maintenance chemotherapy, grade 3 or 4 hematologic toxicity consisted of neutropenia in 82% of patients, leukopenia in 75%, anemia in 10%, and thrombocytopenia in 1%. Grade 3 infection occurred in 31%, including fever and neutropenia in 24%, and grade 3 gastrointestinal adverse events occurred in 5%. Grade 4 nonhematologic toxicity occurred in one patient (neurologic toxicity).
The investigators concluded, “Adding maintenance chemotherapy seems to improve survival for patients with high-risk rhabdomyosarcoma. This approach will be the new standard of care for patients with high-risk rhabdomyosarcoma in future European paediatric soft tissue sarcoma Study Group trials.”
Dr. Bisogno, of the Haematology Oncology Division, Department of Women’s and Children’s Health, University of Padova, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Fondazione Citta della Speranza, Association Leon Berard Enfant Cancereux, Clinical Research Hospital Program (French Ministry of Health), and Cancer Research UK. For full disclosures of the study authors, visit thelancet.com.
