1. Fuerst, Mark L.

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CHICAGO-Maintenance chemotherapy extends life for children with rhabdomyosarcoma, which represents the first treatment advance for this rare cancer in 30 years, according to a new study.

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Rhabdomyosarcoma is a rare tumor of mesenchymal origin typical of childhood, with about 350 children diagnosed in the U.S. and 320 children in the European Union per year.


"Adults may also present with rhabdomyosarcoma. It is a very aggressive tumor, but with modern intensive treatment 70-80 percent of children can be cured," said lead author Gianni Bisogno, MD, PhD, Professor at the University Hospital of Padova in Italy and Chair of the European Paediatric Soft Tissue Sarcoma Study Group. He presented the results of the study at a press conference at the 2018 ASCO Annual Meeting (Abstract LBA2).


The new chemotherapy strategy improves cure rates for children with rhabdomyosarcoma, a rare cancer of the muscle tissue, who are at high risk for cancer recurrence. In a randomized phase III clinical trial, adding 6 months of low-dose maintenance chemotherapy after initial treatment increased the overall survival rate. Children with rhabdomyosarcoma who are alive at 5 years are considered cured, as tumor recurrence is very rare.


"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. 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.


Rhabdomyosarcoma originates in the muscle tissue and can occur in any part of the body, but it is most often found in the head, neck, pelvis, and abdomen. The cancer accounts for 4 percent of all childhood cancers.


The prognosis for rhabdomyosarcoma is generally good, said Bisogno. Modern treatment includes high-dose chemotherapy, radiation, and surgery. However, among children who have metastasis at diagnosis or a recurrence after initial treatment, only 20-30 percent can be cured.


Study Results

The results were reported at the conference on behalf of The European Paediatric Soft Tissue Sarcoma Study Group, which includes 108 centers in 14 countries. The group conducted a randomized maintenance study over more than a 10-year period from April 20, 2006, to Dec. 21, 2016. The study enrolled 371 patients with pathologically proven high-risk rhadomyosarcoma with no evidence of metastasis who were previously untreated.


The patients, ages 6 months to 21 years, were considered at high risk for recurrence due to having large tumors located in a part of the body that is difficult to treat, for example, the head. Most patients were 10 years old or younger (79%).


After completing the standard initial treatment, patients were randomly assigned to either stop treatment (186 patients, the former standard of care) or receive 6 months of maintenance therapy (185 patients) with low doses of two chemotherapy medications, IV vinorelbine and oral cyclophosphamide.


Key Findings

At 5 years from diagnosis, the disease-free survival was 68.8 percent in the standard treatment group versus 77.6 percent in the maintenance group. The 5-year overall survival rates were 73.7 percent with standard therapy and 86.5 percent with maintenance therapy.


The most common side effect in the maintenance group was low blood cell count, though it was usually mild, Bisogno explained. Febrile neutropenia occurred in 25 percent of patients. Infection rates were much lower with maintenance treatment than after initial standard chemotherapy, and neurologic side effects resolved after treatment ended. Long-term side effects are still possible, and patients will continue to be monitored, he noted.


"Maintenance treatment toxicity in comparison with standard treatment showed less anemia, neutropenia, and thrombocytopenia (fewer transfusions); fewer infection episodes; and no cardiac/hepatic/gastrointestinal/renal toxicity," said Bisogno.


The findings of this trial have already changed the standard of care in Europe, where investigators shared the results with soft tissue sarcoma study group institutions. As the standard of care is somewhat different in the U.S., there is a need for further study to understand how to integrate maintenance therapy into existing treatment protocols.


In conclusion, Bisogno noted: "Maintenance therapy represents a novel, well-tolerated effective strategy in patients with high-risk rhabdomyosarcoma. This study establishes the new standard of treatment for patients with high-risk rhabdomyosarcoma, at least in the EU. The same approach is worthwhile to be investigated in other solid tumors of childhood."


ASCO Expert Warren Chow, MD, Clinical Professor, Department of Medical Oncology & Therapeutics Research, at the City of Hope in Duarte, Calif., commented: "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. After 3 decades of research, this finding goes to show that we will continue innovating treatment, no matter how long it takes.


"It took more than 10 years to complete this trial. It is important to have a large trial in a rare disease. We need to determine if the results apply to those who are older than 21 who are at high risk."


Even so, Chow noted that "this is the first significant advance in this cancer in 30 years. No doubt this trial was a home run."


Mark L. Fuerst is a contributing writer.