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CHICAGO -- Adding 6 months of maintenance chemotherapy yielded a 13% increase in the rate of 5-year overall survival in pediatric patients with high-risk rhabdomyosarcoma, results of a phase III study found.

In the RMS2005 Maintenance, the addition of low-dose vinorelbine/cyclophosphamide improved the rate of 5-year overall survival in these patients, from 73.7% to 86.5% (HR 0.52, 95% CI 0.32-0.86, P=0.0111), reported Gianni Bisogno, MD, PhD, of the University Hospital of Padova, Italy, in a plenary session at the American Society of Clinical Oncology (ASCO) annual meeting here.

These tumors are extremely rare, with only 350 children diagnosed with rhabdomyosarcoma in the U.S. each year.

"At the end of this long, not-easy study, we concluded that maintenance is an effective and well-tolerated treatment for children with high-risk rhabdomyosarcoma," said Bisogno, chair of the European Paediatric Soft Tissue Sarcoma Study (EpSSG), during a press briefing here. "And our group decided this is the new standard treatment for patients."

Roughly 70% to 80% of rhabdomyosarcoma patients can be successfully treated with standard therapies, and with recurrences being rare, survival at 5 years is usually considered cure.

"These results will need to be tested in the United States with U.S.-based protocols before becoming standard of care," cautioned ASCO-designated expert Warren Chow, MD, of the City of Hope Comprehensive Cancer Center in Duarte, California.

A number of differences make the applicability of these results in the U.S. uncertain, another specialist explained.

"We use a different backbone," Julia Glade Bender, MD, of New York-Presbyterian Columbia University Medical Center in New York City, told 木瓜直播, pointing out that standard intensive therapy in the U.S. for these patients uses cyclophosphamide rather than ifosfamide, and doxorubicin (which some patients in the trial received) is no longer used here.

Furthermore, the U.S. protocol from the Children's Oncology Group for pediatric rhabdomyosarcoma already calls for a longer duration of treatment than was the standard intensive therapy used by the EpSSG group (42 weeks versus 27 weeks), though shorter now than with the added maintenance therapy (51 weeks).

"It begs the question of whether this is really maintenance therapy or just a longer duration of therapy," said Glade Bender.

To complicate matters, staging is also different abroad, with study participants in the trial being closer to what would be intermediate-risk patients in the U.S. "It's really not directly translatable to practice-change here in the United States," Glade Bender said.

Also, said Chow, "we'll need to determine if these results are applicable to patients older than 21 years of age, who are considered high risk based solely on their age."

Still, he added, "even with these caveats, this is the first significant treatment advance in this rare cancer in more than 30 years."

Since 1972, 20 randomized trials have been conducted in rhabdomyosarcoma, said discussant Douglas Hawkins, MD, of Seattle Children's Hospital. The current trial is "only the third positive randomized study to be reported in pediatric rhabdomyosarcoma."

Glade Bender pointed out that with no control arm, cited by Hawkins was more of a "pick the winner" design and didn't clearly indicate if the better arm was truly adding benefit to these patients, making the current results even more impressive, with it potentially being the . "These studies are incredibly difficult to do," she said.

From 2006 to 2016, RMS2005 Maintenance assessed 670 rhabdomyosarcoma patients for trial eligibility who had high-risk disease (using European staging systems). Patients received standard intensive treatment of high-dose chemotherapy (ifosfamide, vincristine, and actinomycin D with or without doxorubicin) for 9 cycles plus radiotherapy and surgery over a period of 6 to 8 months.

The study then randomized 371 patients who had no evidence of disease on imaging 1:1 to either treatment cessation (n=186) as would have been standard at the time, or to continue on maintenance low-dose metronomic chemotherapy for 6 months (n=185). Intravenous vinorelbine at 25 mg/mq/week and oral cyclophosphamide at 25 mg/mq/day comprised the maintenance regimen.

At 5 years 77.6% of patients were disease free in the maintenance arm versus 69.8% in the control arm (HR 0.68, 95% CI 0.45-1.02, P=0.0613).

The extended treatment was better tolerated and less toxic than the intensive treatment, but not without its own toxicities, which included anemia, neutropenia, and thrombocytopenia. Rate of grade 3 infection was 29%, and while there was still need for transfusions, no cardiac, hepatic, gastrointestinal, or renal toxicity was reported.

Hawkins suggested that the positive results were likely attributable to either vinorelbine, a specific interaction of vinorelbine/cyclophosphamide, or the longer duration of therapy that brought the treatment schedule closer to the 42-week COG protocol.

"One can imagine that we could compare these two strategies to try to tease out whether it's really the duration of therapy rather than maintenance itself that led to the improved overall survival in the EpSSG study," Hawkins said.

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