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CHICAGO – , finds a phase 3 randomized controlled trial of the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG).
Rhabdomyosarcoma is a rare but very aggressive tumor, lead study author Gianni Bisogno, MD, PhD, a professor at the University Hospital of Padova, Italy, and chair of the EpSSG, noted in a press briefing at the annual meeting of the American Society of Clinical Oncology, where the findings were reported. Among pediatric patients who achieve complete response to standard therapy, “we know that after 1 or 2 years, one-third of these children relapse, and most of them die,” he said.
The EpSSG trial, which took about 10 years to conduct, enrolled 371 patients aged 0-21 years with high-risk rhabdomyosarcoma who had had a complete response to standard intensive therapy. They were randomized evenly to stop treatment or to receive 6 months of maintenance treatment consisting of low-dose vinorelbine and cyclophosphamide.
Results reported in the meeting’s plenary session showed that giving maintenance chemotherapy improved the 5-year overall survival rate by an absolute 12.8%, which translated to a near halving of the risk of death. And the maintenance regimen used was generally well tolerated.
“At the end of this long, not-easy study, we concluded that maintenance chemotherapy is an effective and well tolerated treatment for children with high-risk rhabdomyosarcoma,” Dr. Bisogno said.
There are three possibilities for its efficacy, he speculated. “It may be the duration, the type of drugs used, or the metronomic approach. Maybe altogether, these three different actions have a benefit to increase survival.
“Our group has decided this is the new standard treatment for patients. At least in Europe, we give standard intensive therapy and then we continue with 6 more months of low-dose chemotherapy,” Dr. Bisogno concluded. “We think that this approach – a new way of using old drugs – can be of interest also for other pediatric tumors.”
The trial is noteworthy in that it shows “how to successfully conduct large and important trials in rare diseases,” said ASCO Expert Warren Chow, MD.
The standard therapy for rhabdomyosarcomas is somewhat different in the United States, typically a regimen containing vincristine, actinomycin D, cyclophosphamide, and (more recently) irinotecan, he noted. “We have not been traditionally using maintenance chemo for any of the pediatric sarcomas, so this is a paradigm shift. These results will need to be tested with U.S.-based protocols before becoming standard of care in the United States. Also, we will 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.
“Even with these caveats, this is the first significant treatment advance in this rare cancer in more than 30 years,” concluded Dr. Chow, a medical oncologist and clinical professor at City of Hope, Duarte, Calif. “No doubt, this trial was a home run.”
Study details
Patients enrolled in the EpSSG trial had had a complete response to the standard intensive therapy used in Europe: high-dose chemotherapy (ifosfamide, vincristine, and actinomycin D, with or without doxorubicin), radiation therapy, and surgery.
The maintenance chemotherapy consisted of a combination of low-dose intravenous vinorelbine given weekly and oral cyclophosphamide given daily. The 6-month duration was somewhat arbitrary, according to Dr. Bisogno. “We had to start somewhere. So when we started, we decided to use 6 months because there was some evidence in the past for regimens that long. In our next European trial, we are going to test different kinds and durations of maintenance because this is very important.”
The maintenance regimen was well tolerated compared with the regimen given during standard intensive therapy, with, for example, lower rates of grade 3 and 4 anemia (8.9% vs. 48.9%), neutropenia (80.6% vs. 91.6%), and thrombocytopenia (0.6% vs. 26.0%), which translated to less need for transfusions, and a lower rate of grade 3 or 4 infection (29.4% vs. 56.4%), Dr. Bisogno reported. There were no cases of grade 3 or 4 cardiac, hepatobiliary/pancreatic, or renal toxicity.
Relative to peers who stopped treatment after standard intensive therapy, patients who received maintenance treatment tended to have better disease-free survival (77.6% vs. 69.8%; hazard ratio, 0.68; P = .0613) and had significantly better overall survival (86.5% vs. 73.7%; hazard ratio, 0.52; P = .0111).
Dr. Bisogno disclosed that he has a consulting or advisory role with Clinigen Group, and receives travel, accommodations, and/or expenses from Jazz Pharmaceuticals. The study received funding from Fondazione Città della Speranza, Italy.
SOURCE: Bisogno et al. ASCO 2018 Abstract LBA2.
CHICAGO – , finds a phase 3 randomized controlled trial of the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG).
Rhabdomyosarcoma is a rare but very aggressive tumor, lead study author Gianni Bisogno, MD, PhD, a professor at the University Hospital of Padova, Italy, and chair of the EpSSG, noted in a press briefing at the annual meeting of the American Society of Clinical Oncology, where the findings were reported. Among pediatric patients who achieve complete response to standard therapy, “we know that after 1 or 2 years, one-third of these children relapse, and most of them die,” he said.
The EpSSG trial, which took about 10 years to conduct, enrolled 371 patients aged 0-21 years with high-risk rhabdomyosarcoma who had had a complete response to standard intensive therapy. They were randomized evenly to stop treatment or to receive 6 months of maintenance treatment consisting of low-dose vinorelbine and cyclophosphamide.
Results reported in the meeting’s plenary session showed that giving maintenance chemotherapy improved the 5-year overall survival rate by an absolute 12.8%, which translated to a near halving of the risk of death. And the maintenance regimen used was generally well tolerated.
“At the end of this long, not-easy study, we concluded that maintenance chemotherapy is an effective and well tolerated treatment for children with high-risk rhabdomyosarcoma,” Dr. Bisogno said.
There are three possibilities for its efficacy, he speculated. “It may be the duration, the type of drugs used, or the metronomic approach. Maybe altogether, these three different actions have a benefit to increase survival.
“Our group has decided this is the new standard treatment for patients. At least in Europe, we give standard intensive therapy and then we continue with 6 more months of low-dose chemotherapy,” Dr. Bisogno concluded. “We think that this approach – a new way of using old drugs – can be of interest also for other pediatric tumors.”
The trial is noteworthy in that it shows “how to successfully conduct large and important trials in rare diseases,” said ASCO Expert Warren Chow, MD.
The standard therapy for rhabdomyosarcomas is somewhat different in the United States, typically a regimen containing vincristine, actinomycin D, cyclophosphamide, and (more recently) irinotecan, he noted. “We have not been traditionally using maintenance chemo for any of the pediatric sarcomas, so this is a paradigm shift. These results will need to be tested with U.S.-based protocols before becoming standard of care in the United States. Also, we will 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.
“Even with these caveats, this is the first significant treatment advance in this rare cancer in more than 30 years,” concluded Dr. Chow, a medical oncologist and clinical professor at City of Hope, Duarte, Calif. “No doubt, this trial was a home run.”
Study details
Patients enrolled in the EpSSG trial had had a complete response to the standard intensive therapy used in Europe: high-dose chemotherapy (ifosfamide, vincristine, and actinomycin D, with or without doxorubicin), radiation therapy, and surgery.
The maintenance chemotherapy consisted of a combination of low-dose intravenous vinorelbine given weekly and oral cyclophosphamide given daily. The 6-month duration was somewhat arbitrary, according to Dr. Bisogno. “We had to start somewhere. So when we started, we decided to use 6 months because there was some evidence in the past for regimens that long. In our next European trial, we are going to test different kinds and durations of maintenance because this is very important.”
The maintenance regimen was well tolerated compared with the regimen given during standard intensive therapy, with, for example, lower rates of grade 3 and 4 anemia (8.9% vs. 48.9%), neutropenia (80.6% vs. 91.6%), and thrombocytopenia (0.6% vs. 26.0%), which translated to less need for transfusions, and a lower rate of grade 3 or 4 infection (29.4% vs. 56.4%), Dr. Bisogno reported. There were no cases of grade 3 or 4 cardiac, hepatobiliary/pancreatic, or renal toxicity.
Relative to peers who stopped treatment after standard intensive therapy, patients who received maintenance treatment tended to have better disease-free survival (77.6% vs. 69.8%; hazard ratio, 0.68; P = .0613) and had significantly better overall survival (86.5% vs. 73.7%; hazard ratio, 0.52; P = .0111).
Dr. Bisogno disclosed that he has a consulting or advisory role with Clinigen Group, and receives travel, accommodations, and/or expenses from Jazz Pharmaceuticals. The study received funding from Fondazione Città della Speranza, Italy.
SOURCE: Bisogno et al. ASCO 2018 Abstract LBA2.
CHICAGO – , finds a phase 3 randomized controlled trial of the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG).
Rhabdomyosarcoma is a rare but very aggressive tumor, lead study author Gianni Bisogno, MD, PhD, a professor at the University Hospital of Padova, Italy, and chair of the EpSSG, noted in a press briefing at the annual meeting of the American Society of Clinical Oncology, where the findings were reported. Among pediatric patients who achieve complete response to standard therapy, “we know that after 1 or 2 years, one-third of these children relapse, and most of them die,” he said.
The EpSSG trial, which took about 10 years to conduct, enrolled 371 patients aged 0-21 years with high-risk rhabdomyosarcoma who had had a complete response to standard intensive therapy. They were randomized evenly to stop treatment or to receive 6 months of maintenance treatment consisting of low-dose vinorelbine and cyclophosphamide.
Results reported in the meeting’s plenary session showed that giving maintenance chemotherapy improved the 5-year overall survival rate by an absolute 12.8%, which translated to a near halving of the risk of death. And the maintenance regimen used was generally well tolerated.
“At the end of this long, not-easy study, we concluded that maintenance chemotherapy is an effective and well tolerated treatment for children with high-risk rhabdomyosarcoma,” Dr. Bisogno said.
There are three possibilities for its efficacy, he speculated. “It may be the duration, the type of drugs used, or the metronomic approach. Maybe altogether, these three different actions have a benefit to increase survival.
“Our group has decided this is the new standard treatment for patients. At least in Europe, we give standard intensive therapy and then we continue with 6 more months of low-dose chemotherapy,” Dr. Bisogno concluded. “We think that this approach – a new way of using old drugs – can be of interest also for other pediatric tumors.”
The trial is noteworthy in that it shows “how to successfully conduct large and important trials in rare diseases,” said ASCO Expert Warren Chow, MD.
The standard therapy for rhabdomyosarcomas is somewhat different in the United States, typically a regimen containing vincristine, actinomycin D, cyclophosphamide, and (more recently) irinotecan, he noted. “We have not been traditionally using maintenance chemo for any of the pediatric sarcomas, so this is a paradigm shift. These results will need to be tested with U.S.-based protocols before becoming standard of care in the United States. Also, we will 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.
“Even with these caveats, this is the first significant treatment advance in this rare cancer in more than 30 years,” concluded Dr. Chow, a medical oncologist and clinical professor at City of Hope, Duarte, Calif. “No doubt, this trial was a home run.”
Study details
Patients enrolled in the EpSSG trial had had a complete response to the standard intensive therapy used in Europe: high-dose chemotherapy (ifosfamide, vincristine, and actinomycin D, with or without doxorubicin), radiation therapy, and surgery.
The maintenance chemotherapy consisted of a combination of low-dose intravenous vinorelbine given weekly and oral cyclophosphamide given daily. The 6-month duration was somewhat arbitrary, according to Dr. Bisogno. “We had to start somewhere. So when we started, we decided to use 6 months because there was some evidence in the past for regimens that long. In our next European trial, we are going to test different kinds and durations of maintenance because this is very important.”
The maintenance regimen was well tolerated compared with the regimen given during standard intensive therapy, with, for example, lower rates of grade 3 and 4 anemia (8.9% vs. 48.9%), neutropenia (80.6% vs. 91.6%), and thrombocytopenia (0.6% vs. 26.0%), which translated to less need for transfusions, and a lower rate of grade 3 or 4 infection (29.4% vs. 56.4%), Dr. Bisogno reported. There were no cases of grade 3 or 4 cardiac, hepatobiliary/pancreatic, or renal toxicity.
Relative to peers who stopped treatment after standard intensive therapy, patients who received maintenance treatment tended to have better disease-free survival (77.6% vs. 69.8%; hazard ratio, 0.68; P = .0613) and had significantly better overall survival (86.5% vs. 73.7%; hazard ratio, 0.52; P = .0111).
Dr. Bisogno disclosed that he has a consulting or advisory role with Clinigen Group, and receives travel, accommodations, and/or expenses from Jazz Pharmaceuticals. The study received funding from Fondazione Città della Speranza, Italy.
SOURCE: Bisogno et al. ASCO 2018 Abstract LBA2.
REPORTING FROM ASCO 2018
Key clinical point: Six months of maintenance chemotherapy improves survival in youth with high-risk rhabdomyosarcoma.
Major finding: Compared with counterparts not receiving any additional treatment, patients given maintenance low-dose vinorelbine and cyclophosphamide had better 5-year overall survival (86.5% vs. 73.7%; hazard ratio, 0.52).
Study details: A phase 3 randomized controlled trial among 371 patients aged 0-21 years with high-risk rhabdomyosarcoma who had had a complete response to standard intensive therapy.
Disclosures: Dr. Bisogno disclosed that he has a consulting or advisory role with Clinigen Group, and receives travel, accommodations, and/or expenses from Jazz Pharmaceuticals. The study received funding from Fondazione Città della Speranza, Italy.
Source: Bisogno et al. ASCO 2018, Abstract LBA2.