Maintenance chemotherapy could boost survival in paediatric non-metastatic rhabdomyosarcoma
Patients who received maintenance therapy for 6 months after achieving complete remission on standard therapy for non-metastatic rhabdomyosarcoma may have better disease-free survival (DFS) and overall survival (OS) than patients who did not receive maintenance therapy, according to a phase III trial.
“We have been treating rhabdomyosarcoma the same way for more than 30 years, and although different approaches have been tried, this is the first randomized trial in rhabdomyosarcoma to show improved outcomes,” said study lead author Professor Gianni Bisogno from the University Hospital of Padova in Padua, Italy, and chair of the European Paediatric Soft Tissue Sarcoma Study Group.
“Maintenance therapy represents a novel, effective, and well-tolerated strategy in patients with high-risk rhabdomyosarcoma,” said Bisogno.
Study participants were 371 patients aged 0–21 years who were in complete remission following standard therapy for high-risk* non-metastatic rhabdomyosarcoma which included surgery and/or radiotherapy plus chemotherapy including nine cycles of ifosfamide, vincristine, and actinomycin D with or without doxorubicin. They were randomized to receive either no further treatment (standard group; n=186) or low-dose maintenance chemotherapy with intravenous vinorelbine (25 mg/m2 on days 1, 8, and 15 of each 28-day cycle) and oral cyclophosphamide (25 mg/m2/day; n=185) for 6 months. A majority of patients (91 percent) completed maintenance chemotherapy as scheduled, though there were treatment modifications in 79 percent of patients.
Five years after diagnosis, there was a trend towards better DFS among patients who had received maintenance therapy compared with those who had stopped receiving treatment (77.6 percent vs 69.8 percent, hazard ratio [HR], 0.68, 95 percent confidence interval [CI], 0.45–1.02; p=0.0613). [ASCO 2018, abstract LBA2]
OS at 5 years was superior among patients who had received maintenance therapy over those who did not (86.5 percent vs 73.7 percent, HR, 0.52, 95 percent CI, 0.32–0.86; p=0.0111).
In terms of toxicity, infection rates were lower during maintenance therapy than during initial standard treatment (29 percent vs 56 percent). One and two patients experienced grade 3 and 4 neurotoxicity, respectively, but these effects resolved following treatment cessation. Twenty-five percent of patients experienced febrile neutropenia and there were no incidences of grade 3–4 cardiac, hepatobiliary, or renal toxicity.
Overall incidence of myelotoxicity was lower than what is normally seen with standard intensive chemotherapy, said Bisogno.
While 90 percent of patients with high-risk rhabdomyosarcoma achieve complete remission following standard therapy, about 30–40 percent experience relapse, most often within 1 year of remission, and relapse is associated with a high mortality rate, said Bisogno.
“By keeping the pressure on this cancer longer with maintenance therapy, we are giving patients two wins – we are boosting cure rates by preventing relapses and doing so with few serious side effects,” commented ASCO expert Professor Warren Chow from the City of Hope cancer centre in Duarte, California, US.
“By using existing medicines in new ways, we are establishing a new standard of care and, most importantly, we’re helping children and young adults with this rare cancer live longer, with less risk of their cancer returning,” said Bisogno, suggesting that maintenance therapy should be studied, and potentially considered, in other solid tumours in the paediatric population.
“After three decades of research, this finding goes to show that we will continue innovating treatment, no matter how long it takes,” said Chow.