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Low response rate with trofosfamide for advanced STS in elderly
CHICAGO – In elderly patients with previously untreated metastatic soft-tissue sarcomas (STSs), the oral alkylating agent trofosfamide was associated with a lower overall response rate but long-lasting remissions among patients who had complete responses, investigators reported.
In a randomized phase 2 trial that compared trofosfamide with doxorubicin (Adriamycin), the 6-month progression-free survival (PFS) rate with trofosfamide, the primary endpoint, was 27. 6% versus 35.9% in the doxorubicin arm, said Joerg Thomas Hartmann, MD, from Franziskus Hospital in Bielefeld, Germany.
“Median age was 70 years, which means that the population included [patients] 10-15 years older as compared to other trials in metastatic adult sarcoma. The trial met its predefined endpoint, demonstrating that patients treated with trofosfamide attained a 6-month progression-free rate of more than 20%,” he said at the annual meeting of the American Society of Clinical Oncology.
Trofosfamide is an oral alkylating agent chemically related to cyclophosphamide and ifosfamide. It has been evaluated in a variety of hematologic and solid malignancies and has shown particular activity in patients with chemotherapy-naive and treatment-refractory adult STSs.
Dr. Hartmann and his colleagues conducted the phase 2 study to determine whether oral continuous or “metronomic” therapy with trofosfamide could produce a 6-month PFS rate of at least 20% in patients older than 60 years with previously untreated STSs. They selected this rate of 20% or higher based on the European Organisation for Research and Treatment of Cancer (EORTC) target criterion for doxorubicin of 25%.
They also compared grade 3 or greater toxicities of the two regimens, as well as overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) 1,0, and overall survival.
A total of 120 patients with histologically confirmed STSs with no prior first-line chemotherapy and with adequate bone marrow, renal, and liver function were enrolled. The histologies included pleomorphic sarcoma not otherwise specified, leiomyosarcoma, liposarcoma, and others not specified by Dr. Hartmann.
The patients were randomly assigned on a 1:2 basis to receive either intravenous doxorubicin 60 mg/m2 on day 1 of each 21-day cycle for a total of 6 cycles (40 patients) or oral trofosfamide 300 mg/day for days 1 through 7 followed by 150 mg/day until disease progression or unacceptable toxicities (80 patients).
The median patient age in each arm was 70 years.
After a median follow-up of 18.4 months, the trial met its primary endpoint of a 6-months PFS with trofosfamide exceeding 20% (27.6%).
Overall response rates were 7.7% in the doxorubicin arm and 6.6% in the trofosfamide arm.
All three responses in the doxorubicin arm were partial. In the trofosfamide arm there were five responses, including two complete responses and three PR.
The duration of responses in the patients treated with trofosfamide who achieved a complete response were 8.8 and 46.6 months (median, 27.7 months). The median duration of response for trofosfamide-treated patients with a partial response was 8.2 months (range, 1.4-14.9 months).
In contrast, the median duration of response in the patients treated with doxorubicin who achieved a partial response was 4.3 months (range, 2.2-5.6 months).
Grade 3 or 4 adverse events occurred in significantly more patients treated with doxorubicin than they did in patients treated with trofosfamide (61.5% vs. 38.2%, respectively; P = .01). However, deaths within 30 or 60 days of starting on the assigned study drug were higher in the trofosfamide arm (zero vs. two and three vs. six, respectively).
Rates of anemia, leukocytopenia, nausea, and asthenia were similar between the groups, but trofosfamide was significantly associated with higher rates of dyspnea (P = .0148) and fatigue (P = .0264) and with lower rates of neutropenia (P less than .0001) and mucositis (P = .0008).
The trial was supported by Baxter Oncology of Germany. Dr. Hartmann reported having no conflicts of interest to disclose.
SOURCE: Hartman JT et al. ASCO 2018, Abstract 11507.
CHICAGO – In elderly patients with previously untreated metastatic soft-tissue sarcomas (STSs), the oral alkylating agent trofosfamide was associated with a lower overall response rate but long-lasting remissions among patients who had complete responses, investigators reported.
In a randomized phase 2 trial that compared trofosfamide with doxorubicin (Adriamycin), the 6-month progression-free survival (PFS) rate with trofosfamide, the primary endpoint, was 27. 6% versus 35.9% in the doxorubicin arm, said Joerg Thomas Hartmann, MD, from Franziskus Hospital in Bielefeld, Germany.
“Median age was 70 years, which means that the population included [patients] 10-15 years older as compared to other trials in metastatic adult sarcoma. The trial met its predefined endpoint, demonstrating that patients treated with trofosfamide attained a 6-month progression-free rate of more than 20%,” he said at the annual meeting of the American Society of Clinical Oncology.
Trofosfamide is an oral alkylating agent chemically related to cyclophosphamide and ifosfamide. It has been evaluated in a variety of hematologic and solid malignancies and has shown particular activity in patients with chemotherapy-naive and treatment-refractory adult STSs.
Dr. Hartmann and his colleagues conducted the phase 2 study to determine whether oral continuous or “metronomic” therapy with trofosfamide could produce a 6-month PFS rate of at least 20% in patients older than 60 years with previously untreated STSs. They selected this rate of 20% or higher based on the European Organisation for Research and Treatment of Cancer (EORTC) target criterion for doxorubicin of 25%.
They also compared grade 3 or greater toxicities of the two regimens, as well as overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) 1,0, and overall survival.
A total of 120 patients with histologically confirmed STSs with no prior first-line chemotherapy and with adequate bone marrow, renal, and liver function were enrolled. The histologies included pleomorphic sarcoma not otherwise specified, leiomyosarcoma, liposarcoma, and others not specified by Dr. Hartmann.
The patients were randomly assigned on a 1:2 basis to receive either intravenous doxorubicin 60 mg/m2 on day 1 of each 21-day cycle for a total of 6 cycles (40 patients) or oral trofosfamide 300 mg/day for days 1 through 7 followed by 150 mg/day until disease progression or unacceptable toxicities (80 patients).
The median patient age in each arm was 70 years.
After a median follow-up of 18.4 months, the trial met its primary endpoint of a 6-months PFS with trofosfamide exceeding 20% (27.6%).
Overall response rates were 7.7% in the doxorubicin arm and 6.6% in the trofosfamide arm.
All three responses in the doxorubicin arm were partial. In the trofosfamide arm there were five responses, including two complete responses and three PR.
The duration of responses in the patients treated with trofosfamide who achieved a complete response were 8.8 and 46.6 months (median, 27.7 months). The median duration of response for trofosfamide-treated patients with a partial response was 8.2 months (range, 1.4-14.9 months).
In contrast, the median duration of response in the patients treated with doxorubicin who achieved a partial response was 4.3 months (range, 2.2-5.6 months).
Grade 3 or 4 adverse events occurred in significantly more patients treated with doxorubicin than they did in patients treated with trofosfamide (61.5% vs. 38.2%, respectively; P = .01). However, deaths within 30 or 60 days of starting on the assigned study drug were higher in the trofosfamide arm (zero vs. two and three vs. six, respectively).
Rates of anemia, leukocytopenia, nausea, and asthenia were similar between the groups, but trofosfamide was significantly associated with higher rates of dyspnea (P = .0148) and fatigue (P = .0264) and with lower rates of neutropenia (P less than .0001) and mucositis (P = .0008).
The trial was supported by Baxter Oncology of Germany. Dr. Hartmann reported having no conflicts of interest to disclose.
SOURCE: Hartman JT et al. ASCO 2018, Abstract 11507.
CHICAGO – In elderly patients with previously untreated metastatic soft-tissue sarcomas (STSs), the oral alkylating agent trofosfamide was associated with a lower overall response rate but long-lasting remissions among patients who had complete responses, investigators reported.
In a randomized phase 2 trial that compared trofosfamide with doxorubicin (Adriamycin), the 6-month progression-free survival (PFS) rate with trofosfamide, the primary endpoint, was 27. 6% versus 35.9% in the doxorubicin arm, said Joerg Thomas Hartmann, MD, from Franziskus Hospital in Bielefeld, Germany.
“Median age was 70 years, which means that the population included [patients] 10-15 years older as compared to other trials in metastatic adult sarcoma. The trial met its predefined endpoint, demonstrating that patients treated with trofosfamide attained a 6-month progression-free rate of more than 20%,” he said at the annual meeting of the American Society of Clinical Oncology.
Trofosfamide is an oral alkylating agent chemically related to cyclophosphamide and ifosfamide. It has been evaluated in a variety of hematologic and solid malignancies and has shown particular activity in patients with chemotherapy-naive and treatment-refractory adult STSs.
Dr. Hartmann and his colleagues conducted the phase 2 study to determine whether oral continuous or “metronomic” therapy with trofosfamide could produce a 6-month PFS rate of at least 20% in patients older than 60 years with previously untreated STSs. They selected this rate of 20% or higher based on the European Organisation for Research and Treatment of Cancer (EORTC) target criterion for doxorubicin of 25%.
They also compared grade 3 or greater toxicities of the two regimens, as well as overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) 1,0, and overall survival.
A total of 120 patients with histologically confirmed STSs with no prior first-line chemotherapy and with adequate bone marrow, renal, and liver function were enrolled. The histologies included pleomorphic sarcoma not otherwise specified, leiomyosarcoma, liposarcoma, and others not specified by Dr. Hartmann.
The patients were randomly assigned on a 1:2 basis to receive either intravenous doxorubicin 60 mg/m2 on day 1 of each 21-day cycle for a total of 6 cycles (40 patients) or oral trofosfamide 300 mg/day for days 1 through 7 followed by 150 mg/day until disease progression or unacceptable toxicities (80 patients).
The median patient age in each arm was 70 years.
After a median follow-up of 18.4 months, the trial met its primary endpoint of a 6-months PFS with trofosfamide exceeding 20% (27.6%).
Overall response rates were 7.7% in the doxorubicin arm and 6.6% in the trofosfamide arm.
All three responses in the doxorubicin arm were partial. In the trofosfamide arm there were five responses, including two complete responses and three PR.
The duration of responses in the patients treated with trofosfamide who achieved a complete response were 8.8 and 46.6 months (median, 27.7 months). The median duration of response for trofosfamide-treated patients with a partial response was 8.2 months (range, 1.4-14.9 months).
In contrast, the median duration of response in the patients treated with doxorubicin who achieved a partial response was 4.3 months (range, 2.2-5.6 months).
Grade 3 or 4 adverse events occurred in significantly more patients treated with doxorubicin than they did in patients treated with trofosfamide (61.5% vs. 38.2%, respectively; P = .01). However, deaths within 30 or 60 days of starting on the assigned study drug were higher in the trofosfamide arm (zero vs. two and three vs. six, respectively).
Rates of anemia, leukocytopenia, nausea, and asthenia were similar between the groups, but trofosfamide was significantly associated with higher rates of dyspnea (P = .0148) and fatigue (P = .0264) and with lower rates of neutropenia (P less than .0001) and mucositis (P = .0008).
The trial was supported by Baxter Oncology of Germany. Dr. Hartmann reported having no conflicts of interest to disclose.
SOURCE: Hartman JT et al. ASCO 2018, Abstract 11507.
PRESENTED AT ASCO 2018
Key clinical point: The oral alkylating agent trofosfamide showed efficacy in a small number of elderly patients with untreated metastatic soft-tissue sarcomas (STS).
Major finding: The trial met its primary endpoint with a 6-month progression-free survival with trofosfamide of 27.6%
Study details: Randomized phase 2 trial comparing trofosfamide with doxorubicin in elderly patients with previously untreated metastatic STS.
Disclosures: The trial was supported by Baxter Oncology of Germany. Dr. Hartmann reported having no conflicts of interest to disclose.
Source: Hartman JT et al. ASCO 2018, Abstract 11507.
Trabectedin bests supportive care in advanced soft-tissue sarcomas
CHICAGO – Trabectedin (Yondelis) was superior to best supportive care at prolonging progression-free survival in patients with heavily pretreated advanced leiomyosarcomas and liposarcomas, investigators in the randomized phase 3 T-SAR trial reported.
Among 103 patients with soft-tissue sarcomas that had progressed after two to four lines of standard chemotherapy, median progression-free survival (PFS) for patients randomized to trabectedin was 3.12 months, compared with 1.51 for patients randomized to best supportive care.
This difference translated into a hazard ratio (HR) favoring trabectedin of 0.39 (P less than .0001), Axel Le Cesne, MD, of Gustave Roussy Cancer Institute in Villejuif, France, reported on behalf of colleagues in the French Sarcoma Group.
All of the benefit was apparently among patients with what he termed “L-sarcomas” – leiomyosarcoma and liposarcoma – compared with other sarcoma histologies.
“The tumor control rate after six courses of trabectedin is similar to previous studies. As already reported, trabectedin is well-tolerated,” he said at the annual meeting of the American Society of Clinical Oncology.
Trabectedin was shown to be superior to best supportive care at delaying disease progression among patients with advanced translocation-related sarcomas in a randomized phase 2 trial in Japan, but had not been studied in this setting against other sarcoma histologies, Dr. Le Cesne said.
The investigators enrolled 103 patients and randomly assigned them to receive either best supportive care or trabectedin in a 1.5 mg/m2 infusion over 24 hours every 3 weeks. Patients in the best supportive care arm could be crossed over to the trabectedin arm at the time of progression.
Sarcoma histologies included liposarcoma, leiomyosarcoma, undifferentiated sarcomas, myxofibrosarcoma, synovial sarcoma, and others. The L-sarcomas accounted for 60.2% of the patient population.
Fifty-two patients were randomized to trabectedin and 51 to best supportive care, but 2 patients assigned to best supportive care dropped out soon after randomization, leaving 52 and 49 patients, respectively, for the as-treated analysis. All 103 patients were assessable for efficacy.
After a median follow-up of 26 months, median PFS for all patients, as noted before, was 3.12 months in the trabectedin arm and 1.51 months in the best supportive care arm.
The overall response rate in the trabectedin arm was 13.7%, composed of seven partial responses. There were no responses in the best supportive care arm. In all, 66.7% of patients in the trabectedin arm and 61.2% of patients in the best supportive care arm had stable disease, and 19.6% and 38.8%, respectively, had disease progression.
An analysis of PFS by sarcoma histology showed that all of the benefit appeared to be in patients with L-sarcomas, with a median PFS for trabectedin-treated patients of 5.13 months compared with 1.41 months for controls (HR 0.29, P less than .0001).
In contrast, there was no significant difference between the groups among patients with non–L sarcomas, with respective median PFS of 1.81 and 1.51 months (HR 0.60, P = .16). There were no treatment responses among patients in either treatment arm in this subgroup.
Not surprisingly, there were more grade 3 or 4 adverse events among patients in the trabectedin arm. Neutropenia was seen in 23 patients given trabectedin and 1 given best supportive care; leukopenia in 18 patients vs. 0, thrombocytopenia in 13 vs. 0, and elevated liver transaminases in 17 vs. 1, respectively.
In all, 45 of the 49 patients who were treated in the best supportive care arm were crossed over to trabectedin.
Median overall survival was 13.6 months in the trabectedin arm and 10.8 months in the best supportive care arm. This difference was not statistically significant.
Dr Le Cesne noted that the tumor control rate of 30% with trabectedin was similar to that seen in an earlier French trial (Lancet Oncol. 2015 Mar 1;16[3]:312-19).
Pharmamar supplied trabectedin for the study. Dr. Le Cesne disclosed honoraria from the company and from Amgen, Bayer, Lilly, Novartis, and Pfizer.
SOURCE: Le Cesne A et al. ASCO 2018. Abstract 11508.
CHICAGO – Trabectedin (Yondelis) was superior to best supportive care at prolonging progression-free survival in patients with heavily pretreated advanced leiomyosarcomas and liposarcomas, investigators in the randomized phase 3 T-SAR trial reported.
Among 103 patients with soft-tissue sarcomas that had progressed after two to four lines of standard chemotherapy, median progression-free survival (PFS) for patients randomized to trabectedin was 3.12 months, compared with 1.51 for patients randomized to best supportive care.
This difference translated into a hazard ratio (HR) favoring trabectedin of 0.39 (P less than .0001), Axel Le Cesne, MD, of Gustave Roussy Cancer Institute in Villejuif, France, reported on behalf of colleagues in the French Sarcoma Group.
All of the benefit was apparently among patients with what he termed “L-sarcomas” – leiomyosarcoma and liposarcoma – compared with other sarcoma histologies.
“The tumor control rate after six courses of trabectedin is similar to previous studies. As already reported, trabectedin is well-tolerated,” he said at the annual meeting of the American Society of Clinical Oncology.
Trabectedin was shown to be superior to best supportive care at delaying disease progression among patients with advanced translocation-related sarcomas in a randomized phase 2 trial in Japan, but had not been studied in this setting against other sarcoma histologies, Dr. Le Cesne said.
The investigators enrolled 103 patients and randomly assigned them to receive either best supportive care or trabectedin in a 1.5 mg/m2 infusion over 24 hours every 3 weeks. Patients in the best supportive care arm could be crossed over to the trabectedin arm at the time of progression.
Sarcoma histologies included liposarcoma, leiomyosarcoma, undifferentiated sarcomas, myxofibrosarcoma, synovial sarcoma, and others. The L-sarcomas accounted for 60.2% of the patient population.
Fifty-two patients were randomized to trabectedin and 51 to best supportive care, but 2 patients assigned to best supportive care dropped out soon after randomization, leaving 52 and 49 patients, respectively, for the as-treated analysis. All 103 patients were assessable for efficacy.
After a median follow-up of 26 months, median PFS for all patients, as noted before, was 3.12 months in the trabectedin arm and 1.51 months in the best supportive care arm.
The overall response rate in the trabectedin arm was 13.7%, composed of seven partial responses. There were no responses in the best supportive care arm. In all, 66.7% of patients in the trabectedin arm and 61.2% of patients in the best supportive care arm had stable disease, and 19.6% and 38.8%, respectively, had disease progression.
An analysis of PFS by sarcoma histology showed that all of the benefit appeared to be in patients with L-sarcomas, with a median PFS for trabectedin-treated patients of 5.13 months compared with 1.41 months for controls (HR 0.29, P less than .0001).
In contrast, there was no significant difference between the groups among patients with non–L sarcomas, with respective median PFS of 1.81 and 1.51 months (HR 0.60, P = .16). There were no treatment responses among patients in either treatment arm in this subgroup.
Not surprisingly, there were more grade 3 or 4 adverse events among patients in the trabectedin arm. Neutropenia was seen in 23 patients given trabectedin and 1 given best supportive care; leukopenia in 18 patients vs. 0, thrombocytopenia in 13 vs. 0, and elevated liver transaminases in 17 vs. 1, respectively.
In all, 45 of the 49 patients who were treated in the best supportive care arm were crossed over to trabectedin.
Median overall survival was 13.6 months in the trabectedin arm and 10.8 months in the best supportive care arm. This difference was not statistically significant.
Dr Le Cesne noted that the tumor control rate of 30% with trabectedin was similar to that seen in an earlier French trial (Lancet Oncol. 2015 Mar 1;16[3]:312-19).
Pharmamar supplied trabectedin for the study. Dr. Le Cesne disclosed honoraria from the company and from Amgen, Bayer, Lilly, Novartis, and Pfizer.
SOURCE: Le Cesne A et al. ASCO 2018. Abstract 11508.
CHICAGO – Trabectedin (Yondelis) was superior to best supportive care at prolonging progression-free survival in patients with heavily pretreated advanced leiomyosarcomas and liposarcomas, investigators in the randomized phase 3 T-SAR trial reported.
Among 103 patients with soft-tissue sarcomas that had progressed after two to four lines of standard chemotherapy, median progression-free survival (PFS) for patients randomized to trabectedin was 3.12 months, compared with 1.51 for patients randomized to best supportive care.
This difference translated into a hazard ratio (HR) favoring trabectedin of 0.39 (P less than .0001), Axel Le Cesne, MD, of Gustave Roussy Cancer Institute in Villejuif, France, reported on behalf of colleagues in the French Sarcoma Group.
All of the benefit was apparently among patients with what he termed “L-sarcomas” – leiomyosarcoma and liposarcoma – compared with other sarcoma histologies.
“The tumor control rate after six courses of trabectedin is similar to previous studies. As already reported, trabectedin is well-tolerated,” he said at the annual meeting of the American Society of Clinical Oncology.
Trabectedin was shown to be superior to best supportive care at delaying disease progression among patients with advanced translocation-related sarcomas in a randomized phase 2 trial in Japan, but had not been studied in this setting against other sarcoma histologies, Dr. Le Cesne said.
The investigators enrolled 103 patients and randomly assigned them to receive either best supportive care or trabectedin in a 1.5 mg/m2 infusion over 24 hours every 3 weeks. Patients in the best supportive care arm could be crossed over to the trabectedin arm at the time of progression.
Sarcoma histologies included liposarcoma, leiomyosarcoma, undifferentiated sarcomas, myxofibrosarcoma, synovial sarcoma, and others. The L-sarcomas accounted for 60.2% of the patient population.
Fifty-two patients were randomized to trabectedin and 51 to best supportive care, but 2 patients assigned to best supportive care dropped out soon after randomization, leaving 52 and 49 patients, respectively, for the as-treated analysis. All 103 patients were assessable for efficacy.
After a median follow-up of 26 months, median PFS for all patients, as noted before, was 3.12 months in the trabectedin arm and 1.51 months in the best supportive care arm.
The overall response rate in the trabectedin arm was 13.7%, composed of seven partial responses. There were no responses in the best supportive care arm. In all, 66.7% of patients in the trabectedin arm and 61.2% of patients in the best supportive care arm had stable disease, and 19.6% and 38.8%, respectively, had disease progression.
An analysis of PFS by sarcoma histology showed that all of the benefit appeared to be in patients with L-sarcomas, with a median PFS for trabectedin-treated patients of 5.13 months compared with 1.41 months for controls (HR 0.29, P less than .0001).
In contrast, there was no significant difference between the groups among patients with non–L sarcomas, with respective median PFS of 1.81 and 1.51 months (HR 0.60, P = .16). There were no treatment responses among patients in either treatment arm in this subgroup.
Not surprisingly, there were more grade 3 or 4 adverse events among patients in the trabectedin arm. Neutropenia was seen in 23 patients given trabectedin and 1 given best supportive care; leukopenia in 18 patients vs. 0, thrombocytopenia in 13 vs. 0, and elevated liver transaminases in 17 vs. 1, respectively.
In all, 45 of the 49 patients who were treated in the best supportive care arm were crossed over to trabectedin.
Median overall survival was 13.6 months in the trabectedin arm and 10.8 months in the best supportive care arm. This difference was not statistically significant.
Dr Le Cesne noted that the tumor control rate of 30% with trabectedin was similar to that seen in an earlier French trial (Lancet Oncol. 2015 Mar 1;16[3]:312-19).
Pharmamar supplied trabectedin for the study. Dr. Le Cesne disclosed honoraria from the company and from Amgen, Bayer, Lilly, Novartis, and Pfizer.
SOURCE: Le Cesne A et al. ASCO 2018. Abstract 11508.
REPORTING FROM ASCO 2018
Key clinical point: Trabectedin was superior to best supportive care in delaying disease progression among patients with advanced soft tissue sarcomas.
Major finding: Median progression-free survival for patients with leiomyosarcoma or liposarcoma treated with trabectedin was 5.13 months vs. 1.41 months for patients treated with best supportive care.
Study details: Randomized open-label trial of 103 patients with histologically proven advanced soft-tissue sarcoma who progressed after at least 1 anthracycline-containing regimen.
Disclosures: Pharmamar supplied trabectedin for the study. Dr. Le Cesne disclosed receiving honoraria from the company and from Amgen, Bayer, Lilly, Novartis, and Pfizer.
Source: Le Cesne A et al. ASCO 2018. Abstract 11508.
DESMOPAZ: Pazopanib slows disease progression of desmoid tumors
Pazopanib elicited clinically meaningful responses in adults with progressive desmoid tumors according to RECIST 1.1 criteria, based on two imaging studies within a 6-month interval in the phase 2 DESMOPAZ trial.
“Pazopanib has meaningful clinical activity in patients with progressive desmoid tumors,” Maud Toulmonde, MD, of the Institut Bergonié, Bordeaux, France, reported at the annual meeting of the American Society of Clinical Oncology.
Patients were accrued for the study at 12 centers of the French Sarcoma Group and were randomly assigned to receive either oral pazopanib 800 mg/day or methotrexate (30 mg/m²) plus vinblastine (5 mg/m²) given intravenously once a week for 6 months and then every 15 days for 6 months. Treatment was administered until disease progressed (these patients were allowed to cross over to pazopanib) or patients had unacceptable toxicity. Maximum treatment time was one year.
Based on central pathological and radiological review, tumors shrank in 38 of 46 assessable patients (82.6%) given pazopanib. A partial response was seen in 17 patients (37%) and stable disease was observed in 21 patients (45.7%).
In the patients given methotrexate plus vinblastine, tumors shrank in 11 of 20 assessable patients (55%), resulting in partial responses in 5 (25%) and stable disease in 6 (30%).
The 6-month non-progressive disease rate was 86% (95% CI = 72.1-94.7) in the pazopanib-treated patients (37/43) and 50% (95% CI = 27.2-72.8) in the methotrexate plus vinblastine-treated patients (10/20).
Dr. Toulmonde and most of her co-authors had no relevant financial disclosures. Some authors disclosed funding from a wide range of drug companies including Novartis, the maker of pazopanib (Votrient). Clinical trial information: NCT01876082
SOURCE: Toulmonde M et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11501.
Pazopanib elicited clinically meaningful responses in adults with progressive desmoid tumors according to RECIST 1.1 criteria, based on two imaging studies within a 6-month interval in the phase 2 DESMOPAZ trial.
“Pazopanib has meaningful clinical activity in patients with progressive desmoid tumors,” Maud Toulmonde, MD, of the Institut Bergonié, Bordeaux, France, reported at the annual meeting of the American Society of Clinical Oncology.
Patients were accrued for the study at 12 centers of the French Sarcoma Group and were randomly assigned to receive either oral pazopanib 800 mg/day or methotrexate (30 mg/m²) plus vinblastine (5 mg/m²) given intravenously once a week for 6 months and then every 15 days for 6 months. Treatment was administered until disease progressed (these patients were allowed to cross over to pazopanib) or patients had unacceptable toxicity. Maximum treatment time was one year.
Based on central pathological and radiological review, tumors shrank in 38 of 46 assessable patients (82.6%) given pazopanib. A partial response was seen in 17 patients (37%) and stable disease was observed in 21 patients (45.7%).
In the patients given methotrexate plus vinblastine, tumors shrank in 11 of 20 assessable patients (55%), resulting in partial responses in 5 (25%) and stable disease in 6 (30%).
The 6-month non-progressive disease rate was 86% (95% CI = 72.1-94.7) in the pazopanib-treated patients (37/43) and 50% (95% CI = 27.2-72.8) in the methotrexate plus vinblastine-treated patients (10/20).
Dr. Toulmonde and most of her co-authors had no relevant financial disclosures. Some authors disclosed funding from a wide range of drug companies including Novartis, the maker of pazopanib (Votrient). Clinical trial information: NCT01876082
SOURCE: Toulmonde M et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11501.
Pazopanib elicited clinically meaningful responses in adults with progressive desmoid tumors according to RECIST 1.1 criteria, based on two imaging studies within a 6-month interval in the phase 2 DESMOPAZ trial.
“Pazopanib has meaningful clinical activity in patients with progressive desmoid tumors,” Maud Toulmonde, MD, of the Institut Bergonié, Bordeaux, France, reported at the annual meeting of the American Society of Clinical Oncology.
Patients were accrued for the study at 12 centers of the French Sarcoma Group and were randomly assigned to receive either oral pazopanib 800 mg/day or methotrexate (30 mg/m²) plus vinblastine (5 mg/m²) given intravenously once a week for 6 months and then every 15 days for 6 months. Treatment was administered until disease progressed (these patients were allowed to cross over to pazopanib) or patients had unacceptable toxicity. Maximum treatment time was one year.
Based on central pathological and radiological review, tumors shrank in 38 of 46 assessable patients (82.6%) given pazopanib. A partial response was seen in 17 patients (37%) and stable disease was observed in 21 patients (45.7%).
In the patients given methotrexate plus vinblastine, tumors shrank in 11 of 20 assessable patients (55%), resulting in partial responses in 5 (25%) and stable disease in 6 (30%).
The 6-month non-progressive disease rate was 86% (95% CI = 72.1-94.7) in the pazopanib-treated patients (37/43) and 50% (95% CI = 27.2-72.8) in the methotrexate plus vinblastine-treated patients (10/20).
Dr. Toulmonde and most of her co-authors had no relevant financial disclosures. Some authors disclosed funding from a wide range of drug companies including Novartis, the maker of pazopanib (Votrient). Clinical trial information: NCT01876082
SOURCE: Toulmonde M et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11501.
FROM ASCO 2018
Metastatic soft tissue sarcomas respond to anlotinib
Anlotinib was confirmed to be safe and effective for soft tissue sarcoma patients who have progressed after first-line chemotherapy, based on results of a randomized, placebo-controlled, multicenter trial of patients in China.
“Anlotinib is a new treatment option for patients with advanced STS after failure of standard chemotherapy,” Yihebali Chi, MD, of the National Cancer Center/Cancer Hospital in Beijing, China, reported at the annual meeting of the American Society of Clinical Oncology.
In a study of patients with disease progression after first-line therapy, the median progression-free survival (PFS) was 6.3 months (95% CI: 4.3-8.4) with anlotinib and 1.5 months (95% CI: 1.43-1.57) with placebo (HR=0.33, P less than 0.0001). The objective response rate was 10.13% for anlotinib and 1.33% for placebo (P = 0.0145); disease control rate was 55.7% versus 22.67% (P less than 0.0001).
For 57 patients with synovial sarcomas, the median PFS was 5.73 months versus 1.43 months (HR = 0.2, P less than 0.0001). For 56 patients with alveolar soft part sarcomas, the median PFS was 18.23 months versus 3 months (HR = 0.14, P less than 0.0001). For 41 patients with leiomyosarcomas, the median PFS was 5.83 months versus 1.43 months (HR = 0.19, P less than 0.0001).
The most common grade 3 or higher adverse events were hypertension (19% with anlotinib versus 0 with placebo), gamma glutamyl transferase elevation (4.4% versus 1.3%), triglyceride increase (4.4% versus 0), low density lipoprotein elevation (3.2% versus 2.7%), hyponatremia (3.2% versus 1.3%) and neutrophil count reduction (3.2% versus 0).
The study included 233 patients aged 18 years and older with angiogenesis inhibitor naive, histologically proven advanced soft tissue sarcomas, intolerance or failure to respond to anthracycline-based chemotherapy, and at least one measurable lesion according to RECIST 1.1. Subjects were randomly assigned (2:1) to receive anlotinib (12 mg per day, 2 weeks on and 1 week off) or to placebo. Anlotinib was given to 158 patients and placebo to 75.
The authors disclosed having no relevant financial relationships. Clinical trial information: NCT02449343
SOURCE: Chi Y et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology, Abstract 11503.
Anlotinib was confirmed to be safe and effective for soft tissue sarcoma patients who have progressed after first-line chemotherapy, based on results of a randomized, placebo-controlled, multicenter trial of patients in China.
“Anlotinib is a new treatment option for patients with advanced STS after failure of standard chemotherapy,” Yihebali Chi, MD, of the National Cancer Center/Cancer Hospital in Beijing, China, reported at the annual meeting of the American Society of Clinical Oncology.
In a study of patients with disease progression after first-line therapy, the median progression-free survival (PFS) was 6.3 months (95% CI: 4.3-8.4) with anlotinib and 1.5 months (95% CI: 1.43-1.57) with placebo (HR=0.33, P less than 0.0001). The objective response rate was 10.13% for anlotinib and 1.33% for placebo (P = 0.0145); disease control rate was 55.7% versus 22.67% (P less than 0.0001).
For 57 patients with synovial sarcomas, the median PFS was 5.73 months versus 1.43 months (HR = 0.2, P less than 0.0001). For 56 patients with alveolar soft part sarcomas, the median PFS was 18.23 months versus 3 months (HR = 0.14, P less than 0.0001). For 41 patients with leiomyosarcomas, the median PFS was 5.83 months versus 1.43 months (HR = 0.19, P less than 0.0001).
The most common grade 3 or higher adverse events were hypertension (19% with anlotinib versus 0 with placebo), gamma glutamyl transferase elevation (4.4% versus 1.3%), triglyceride increase (4.4% versus 0), low density lipoprotein elevation (3.2% versus 2.7%), hyponatremia (3.2% versus 1.3%) and neutrophil count reduction (3.2% versus 0).
The study included 233 patients aged 18 years and older with angiogenesis inhibitor naive, histologically proven advanced soft tissue sarcomas, intolerance or failure to respond to anthracycline-based chemotherapy, and at least one measurable lesion according to RECIST 1.1. Subjects were randomly assigned (2:1) to receive anlotinib (12 mg per day, 2 weeks on and 1 week off) or to placebo. Anlotinib was given to 158 patients and placebo to 75.
The authors disclosed having no relevant financial relationships. Clinical trial information: NCT02449343
SOURCE: Chi Y et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology, Abstract 11503.
Anlotinib was confirmed to be safe and effective for soft tissue sarcoma patients who have progressed after first-line chemotherapy, based on results of a randomized, placebo-controlled, multicenter trial of patients in China.
“Anlotinib is a new treatment option for patients with advanced STS after failure of standard chemotherapy,” Yihebali Chi, MD, of the National Cancer Center/Cancer Hospital in Beijing, China, reported at the annual meeting of the American Society of Clinical Oncology.
In a study of patients with disease progression after first-line therapy, the median progression-free survival (PFS) was 6.3 months (95% CI: 4.3-8.4) with anlotinib and 1.5 months (95% CI: 1.43-1.57) with placebo (HR=0.33, P less than 0.0001). The objective response rate was 10.13% for anlotinib and 1.33% for placebo (P = 0.0145); disease control rate was 55.7% versus 22.67% (P less than 0.0001).
For 57 patients with synovial sarcomas, the median PFS was 5.73 months versus 1.43 months (HR = 0.2, P less than 0.0001). For 56 patients with alveolar soft part sarcomas, the median PFS was 18.23 months versus 3 months (HR = 0.14, P less than 0.0001). For 41 patients with leiomyosarcomas, the median PFS was 5.83 months versus 1.43 months (HR = 0.19, P less than 0.0001).
The most common grade 3 or higher adverse events were hypertension (19% with anlotinib versus 0 with placebo), gamma glutamyl transferase elevation (4.4% versus 1.3%), triglyceride increase (4.4% versus 0), low density lipoprotein elevation (3.2% versus 2.7%), hyponatremia (3.2% versus 1.3%) and neutrophil count reduction (3.2% versus 0).
The study included 233 patients aged 18 years and older with angiogenesis inhibitor naive, histologically proven advanced soft tissue sarcomas, intolerance or failure to respond to anthracycline-based chemotherapy, and at least one measurable lesion according to RECIST 1.1. Subjects were randomly assigned (2:1) to receive anlotinib (12 mg per day, 2 weeks on and 1 week off) or to placebo. Anlotinib was given to 158 patients and placebo to 75.
The authors disclosed having no relevant financial relationships. Clinical trial information: NCT02449343
SOURCE: Chi Y et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology, Abstract 11503.
FROM ASCO 2018
REGOBONE: Regorafenib shows efficacy in metastatic osteosarcoma
Regorafenib appears to be active in patients with metastatic osteosarcomas, based on results from REGOBONE a non-comparative phase 2, double-blind, placebo-controlled trial.
Among 38 efficacy-evaluable patients (12 given placebo and 26 given regorafenib), 17 patients (65.4%) were non-progressive at 8 weeks in the regorafenib arm and 0 in the placebo arm, Florence Duffaud, MD, of La Timone University Hospital, Marseille, France, reported at the annual meeting of the American Society of Clinical Oncology.
Median progression-free survival (PFS) was 13.7 weeks for patients given regorafenib and 4 weeks for those given placebo. The PFS rate at 24 weeks was 35% with regorafenib and 0 with placebo. The 1-year overall survival was 53% and 33% for regorafenib and placebo, respectively.
Ten patients in the placebo arm crossed-over to the regorafenib arm of the study after centrally-confirmed disease progression. The most common adverse events of Grade 3 or greater with regorafenib were hypertension (24%), hand-foot skin reaction (17%), asthenia (10%), and diarrhea (7%).
REGOBONE consists of 4 independent cohorts: patients with either metastatic osteosarcoma, Ewing sarcoma, chondrosarcoma, or chordoma. The results were reported for 43 patients with metastatic osteosarcoma who were randomized 2:1 to receive either regorafinib (160 mg/day for 21 days of a 28 day cycle) or to placebo with the option to cross over at the time of confirmed central review of progressive disease.
Dr. Duffaud and several of her co-authors received funding from various drug companies including Bayer, the maker of regorafenib (Stivarga). Clinical trial information: NCT02389244
SOURCE: Duffaud F et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11504.
Regorafenib appears to be active in patients with metastatic osteosarcomas, based on results from REGOBONE a non-comparative phase 2, double-blind, placebo-controlled trial.
Among 38 efficacy-evaluable patients (12 given placebo and 26 given regorafenib), 17 patients (65.4%) were non-progressive at 8 weeks in the regorafenib arm and 0 in the placebo arm, Florence Duffaud, MD, of La Timone University Hospital, Marseille, France, reported at the annual meeting of the American Society of Clinical Oncology.
Median progression-free survival (PFS) was 13.7 weeks for patients given regorafenib and 4 weeks for those given placebo. The PFS rate at 24 weeks was 35% with regorafenib and 0 with placebo. The 1-year overall survival was 53% and 33% for regorafenib and placebo, respectively.
Ten patients in the placebo arm crossed-over to the regorafenib arm of the study after centrally-confirmed disease progression. The most common adverse events of Grade 3 or greater with regorafenib were hypertension (24%), hand-foot skin reaction (17%), asthenia (10%), and diarrhea (7%).
REGOBONE consists of 4 independent cohorts: patients with either metastatic osteosarcoma, Ewing sarcoma, chondrosarcoma, or chordoma. The results were reported for 43 patients with metastatic osteosarcoma who were randomized 2:1 to receive either regorafinib (160 mg/day for 21 days of a 28 day cycle) or to placebo with the option to cross over at the time of confirmed central review of progressive disease.
Dr. Duffaud and several of her co-authors received funding from various drug companies including Bayer, the maker of regorafenib (Stivarga). Clinical trial information: NCT02389244
SOURCE: Duffaud F et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11504.
Regorafenib appears to be active in patients with metastatic osteosarcomas, based on results from REGOBONE a non-comparative phase 2, double-blind, placebo-controlled trial.
Among 38 efficacy-evaluable patients (12 given placebo and 26 given regorafenib), 17 patients (65.4%) were non-progressive at 8 weeks in the regorafenib arm and 0 in the placebo arm, Florence Duffaud, MD, of La Timone University Hospital, Marseille, France, reported at the annual meeting of the American Society of Clinical Oncology.
Median progression-free survival (PFS) was 13.7 weeks for patients given regorafenib and 4 weeks for those given placebo. The PFS rate at 24 weeks was 35% with regorafenib and 0 with placebo. The 1-year overall survival was 53% and 33% for regorafenib and placebo, respectively.
Ten patients in the placebo arm crossed-over to the regorafenib arm of the study after centrally-confirmed disease progression. The most common adverse events of Grade 3 or greater with regorafenib were hypertension (24%), hand-foot skin reaction (17%), asthenia (10%), and diarrhea (7%).
REGOBONE consists of 4 independent cohorts: patients with either metastatic osteosarcoma, Ewing sarcoma, chondrosarcoma, or chordoma. The results were reported for 43 patients with metastatic osteosarcoma who were randomized 2:1 to receive either regorafinib (160 mg/day for 21 days of a 28 day cycle) or to placebo with the option to cross over at the time of confirmed central review of progressive disease.
Dr. Duffaud and several of her co-authors received funding from various drug companies including Bayer, the maker of regorafenib (Stivarga). Clinical trial information: NCT02389244
SOURCE: Duffaud F et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11504.
FROM ASCO 2018
Sorafenib boosts PFS in desmoid tumor patients
Sorafenib was well tolerated with significantly improved progression-free survival in select patients with desmoid tumors, reported Mrinal M. Gounder, MD, of Memorial Sloan-Kettering Cancer Center, New York.
“The study exceeded its primary endpoint for progression-free survival ... Sorafenib may represent a new, first-line or subsequent-line standard of care in select patients with desmoid tumors,” Dr. Gounder said at the annual meeting of the American Society of Clinical Oncology.
For this international prospective study of progression-free survival response to sorafenib, 87 patients were enrolled over 17 months at 25 sites. Patients had unresectable progressive or symptomatic desmoid tumors. Patients were stratified by pain level and disease site and randomized 2:1 to sorafenib 400 mg/day or placebo. Placebo-treated patients were crossed over to sorafenib if they reached RECIST 1.1.
After a median follow up for 26 months, disease had progressed in 22 of 32 patients on placebo and in 7 of 43 patients on sorafenib. One sorafenib-treated patient died. Durable partial responses were seen in 14 of 43 on sorafenib and in 7 of 32 on placebo. At one year, progression-free survival was 43% with placebo (median PFS 9.4 months) and 87% with sorafenib (median PFS not reached [HR = 0.14 (95% CI 0.06-0.33), P less than 0.0001)].
The authors disclosed funding from a wide range of drug companies. Several authors received funding from Bayer, the maker of sorafenib (Nexavar). Clinical trial information: NCT02066181.
SOURCE: Gounder M et al. ASCO 2018 (the annual meeting of the American Society of Clinical Oncology), Abstract 11500.
Sorafenib was well tolerated with significantly improved progression-free survival in select patients with desmoid tumors, reported Mrinal M. Gounder, MD, of Memorial Sloan-Kettering Cancer Center, New York.
“The study exceeded its primary endpoint for progression-free survival ... Sorafenib may represent a new, first-line or subsequent-line standard of care in select patients with desmoid tumors,” Dr. Gounder said at the annual meeting of the American Society of Clinical Oncology.
For this international prospective study of progression-free survival response to sorafenib, 87 patients were enrolled over 17 months at 25 sites. Patients had unresectable progressive or symptomatic desmoid tumors. Patients were stratified by pain level and disease site and randomized 2:1 to sorafenib 400 mg/day or placebo. Placebo-treated patients were crossed over to sorafenib if they reached RECIST 1.1.
After a median follow up for 26 months, disease had progressed in 22 of 32 patients on placebo and in 7 of 43 patients on sorafenib. One sorafenib-treated patient died. Durable partial responses were seen in 14 of 43 on sorafenib and in 7 of 32 on placebo. At one year, progression-free survival was 43% with placebo (median PFS 9.4 months) and 87% with sorafenib (median PFS not reached [HR = 0.14 (95% CI 0.06-0.33), P less than 0.0001)].
The authors disclosed funding from a wide range of drug companies. Several authors received funding from Bayer, the maker of sorafenib (Nexavar). Clinical trial information: NCT02066181.
SOURCE: Gounder M et al. ASCO 2018 (the annual meeting of the American Society of Clinical Oncology), Abstract 11500.
Sorafenib was well tolerated with significantly improved progression-free survival in select patients with desmoid tumors, reported Mrinal M. Gounder, MD, of Memorial Sloan-Kettering Cancer Center, New York.
“The study exceeded its primary endpoint for progression-free survival ... Sorafenib may represent a new, first-line or subsequent-line standard of care in select patients with desmoid tumors,” Dr. Gounder said at the annual meeting of the American Society of Clinical Oncology.
For this international prospective study of progression-free survival response to sorafenib, 87 patients were enrolled over 17 months at 25 sites. Patients had unresectable progressive or symptomatic desmoid tumors. Patients were stratified by pain level and disease site and randomized 2:1 to sorafenib 400 mg/day or placebo. Placebo-treated patients were crossed over to sorafenib if they reached RECIST 1.1.
After a median follow up for 26 months, disease had progressed in 22 of 32 patients on placebo and in 7 of 43 patients on sorafenib. One sorafenib-treated patient died. Durable partial responses were seen in 14 of 43 on sorafenib and in 7 of 32 on placebo. At one year, progression-free survival was 43% with placebo (median PFS 9.4 months) and 87% with sorafenib (median PFS not reached [HR = 0.14 (95% CI 0.06-0.33), P less than 0.0001)].
The authors disclosed funding from a wide range of drug companies. Several authors received funding from Bayer, the maker of sorafenib (Nexavar). Clinical trial information: NCT02066181.
SOURCE: Gounder M et al. ASCO 2018 (the annual meeting of the American Society of Clinical Oncology), Abstract 11500.
FROM ASCO 2018
SARCO24: Regorafenib falls short for treatment-refractory liposarcoma
Regorafenib fell short of improving progression-free survival in patients with treatment-refractory liposarcomas, Richard Reidel, MD, of Duke University Medical Center, Durham, N.C., reported at the annual meeting of the American Society of Clinical Oncology.
In a 48-patient study, the median progression-free survival was not significantly different for regorafenib-treated patients, 1.9 months, and for placebo-treated patients, 2.1 months. None of the regorafenib-treated patients had responses. Median overall survival was not reached for either group of patients.
The most common grade 3-4 adverse events observed with regorafenib included: grade 3 abdominal pain (13%), hypertension (13%), rash (13%), anemia (8%), anorexia (8%), generalized weakness (8%), and elevated lipase (8%). Grade 5 events occurred in one patient on regorafenib and 3 on placebo.
For the study, patients with advanced or metastatic, treatment-refractory liposarcoma were randomized 1:1 to receive either regorafenib 160 mg daily or placebo (3 weeks on, 1 week off). The study was powered to detect a difference of at least 3 months in median progression-free survival. Secondary objectives included adverse event assessments, overall response rate, time to tumor progression, progression-free survival at 8 and 16 weeks, overall survival, and disease-specific survival. Follow up information was available for 47 patients, with a median follow up of 3.8 months (0.2-15.3). The analyses included 33 dedifferentiated, 12 myxoid/round cell and 2 pleomorphic liposarcomas.
Dr. Riedel, and some of his co-authors, disclosed financial relationships with several drug companies including Bayer, the maker of regorafenib (Stivarga). Clinical trial information: NCT02048371
SOURCE: Riedel R et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11505.
Regorafenib fell short of improving progression-free survival in patients with treatment-refractory liposarcomas, Richard Reidel, MD, of Duke University Medical Center, Durham, N.C., reported at the annual meeting of the American Society of Clinical Oncology.
In a 48-patient study, the median progression-free survival was not significantly different for regorafenib-treated patients, 1.9 months, and for placebo-treated patients, 2.1 months. None of the regorafenib-treated patients had responses. Median overall survival was not reached for either group of patients.
The most common grade 3-4 adverse events observed with regorafenib included: grade 3 abdominal pain (13%), hypertension (13%), rash (13%), anemia (8%), anorexia (8%), generalized weakness (8%), and elevated lipase (8%). Grade 5 events occurred in one patient on regorafenib and 3 on placebo.
For the study, patients with advanced or metastatic, treatment-refractory liposarcoma were randomized 1:1 to receive either regorafenib 160 mg daily or placebo (3 weeks on, 1 week off). The study was powered to detect a difference of at least 3 months in median progression-free survival. Secondary objectives included adverse event assessments, overall response rate, time to tumor progression, progression-free survival at 8 and 16 weeks, overall survival, and disease-specific survival. Follow up information was available for 47 patients, with a median follow up of 3.8 months (0.2-15.3). The analyses included 33 dedifferentiated, 12 myxoid/round cell and 2 pleomorphic liposarcomas.
Dr. Riedel, and some of his co-authors, disclosed financial relationships with several drug companies including Bayer, the maker of regorafenib (Stivarga). Clinical trial information: NCT02048371
SOURCE: Riedel R et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11505.
Regorafenib fell short of improving progression-free survival in patients with treatment-refractory liposarcomas, Richard Reidel, MD, of Duke University Medical Center, Durham, N.C., reported at the annual meeting of the American Society of Clinical Oncology.
In a 48-patient study, the median progression-free survival was not significantly different for regorafenib-treated patients, 1.9 months, and for placebo-treated patients, 2.1 months. None of the regorafenib-treated patients had responses. Median overall survival was not reached for either group of patients.
The most common grade 3-4 adverse events observed with regorafenib included: grade 3 abdominal pain (13%), hypertension (13%), rash (13%), anemia (8%), anorexia (8%), generalized weakness (8%), and elevated lipase (8%). Grade 5 events occurred in one patient on regorafenib and 3 on placebo.
For the study, patients with advanced or metastatic, treatment-refractory liposarcoma were randomized 1:1 to receive either regorafenib 160 mg daily or placebo (3 weeks on, 1 week off). The study was powered to detect a difference of at least 3 months in median progression-free survival. Secondary objectives included adverse event assessments, overall response rate, time to tumor progression, progression-free survival at 8 and 16 weeks, overall survival, and disease-specific survival. Follow up information was available for 47 patients, with a median follow up of 3.8 months (0.2-15.3). The analyses included 33 dedifferentiated, 12 myxoid/round cell and 2 pleomorphic liposarcomas.
Dr. Riedel, and some of his co-authors, disclosed financial relationships with several drug companies including Bayer, the maker of regorafenib (Stivarga). Clinical trial information: NCT02048371
SOURCE: Riedel R et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11505.
FROM ASCO 2018
EPAZ: Pazopanib matches doxorubicin without the neutropenia in elderly patients
Pazopanib can be considered as a first line alternative treatment to doxorubicin in patients over age 60 with advanced, inoperable soft tissue sarcomas, based on the results of the phase 2 EPAZ study presented at the annual meeting of the American Society of Clinical Oncology.
Pazopanib outcomes compared to those with doxorubicin in the study; but unlike doxorubicin, pazopanib was not associated with neutropenia, reported Viktor Grünwald, MD, of the Medical School Hanover, Germany. “The distinct AE (adverse event) profile may be used to council patients and tailor therapy to individual needs.”
In the randomized study with a median 12-month follow up of previously untreated patients with a median age of 71 years, the incidence of grade 4 neutropenia and neutropenic fever were 56% and 10% for 39 patients given doxorubicin and 0% and 0% for 81 patients given pazopanib, respectively. Overall survival was 14.3 months and 12.3 months, a nonsignificant difference. The most frequent adverse events for doxorubicin were fatigue (64.9%), alopecia (56.8%) and nausea (48.6%), and for pazopanib they were fatigue (58%), nausea (43.2%) and diarrhea (43.2%). Similar outcomes were reported for global EORTC QLQ-C30 measures.
EPAZ included patients aged 60 years and older (median 71 years) with no prior systemic treatment for soft tissue sarcoma, progressive disease, ECOG 0-2, and adequate organ function. After 1:2 randomization, patients received either doxorubicin 75 mg/m2 every 3 weeks for a total of 6 cycles or oral pazopanib 800 mg/day given continuously. ECOG 2 and liposarcoma histology were used for stratification.
Dr. Grunwald and several of his co-authors disclosed financial relationships with various drug companies including Novartis, the maker of pazopanib (Votrient). Clinical trial information: NCT01861951
SOURCE: Grunwald V et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11506.
Pazopanib can be considered as a first line alternative treatment to doxorubicin in patients over age 60 with advanced, inoperable soft tissue sarcomas, based on the results of the phase 2 EPAZ study presented at the annual meeting of the American Society of Clinical Oncology.
Pazopanib outcomes compared to those with doxorubicin in the study; but unlike doxorubicin, pazopanib was not associated with neutropenia, reported Viktor Grünwald, MD, of the Medical School Hanover, Germany. “The distinct AE (adverse event) profile may be used to council patients and tailor therapy to individual needs.”
In the randomized study with a median 12-month follow up of previously untreated patients with a median age of 71 years, the incidence of grade 4 neutropenia and neutropenic fever were 56% and 10% for 39 patients given doxorubicin and 0% and 0% for 81 patients given pazopanib, respectively. Overall survival was 14.3 months and 12.3 months, a nonsignificant difference. The most frequent adverse events for doxorubicin were fatigue (64.9%), alopecia (56.8%) and nausea (48.6%), and for pazopanib they were fatigue (58%), nausea (43.2%) and diarrhea (43.2%). Similar outcomes were reported for global EORTC QLQ-C30 measures.
EPAZ included patients aged 60 years and older (median 71 years) with no prior systemic treatment for soft tissue sarcoma, progressive disease, ECOG 0-2, and adequate organ function. After 1:2 randomization, patients received either doxorubicin 75 mg/m2 every 3 weeks for a total of 6 cycles or oral pazopanib 800 mg/day given continuously. ECOG 2 and liposarcoma histology were used for stratification.
Dr. Grunwald and several of his co-authors disclosed financial relationships with various drug companies including Novartis, the maker of pazopanib (Votrient). Clinical trial information: NCT01861951
SOURCE: Grunwald V et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11506.
Pazopanib can be considered as a first line alternative treatment to doxorubicin in patients over age 60 with advanced, inoperable soft tissue sarcomas, based on the results of the phase 2 EPAZ study presented at the annual meeting of the American Society of Clinical Oncology.
Pazopanib outcomes compared to those with doxorubicin in the study; but unlike doxorubicin, pazopanib was not associated with neutropenia, reported Viktor Grünwald, MD, of the Medical School Hanover, Germany. “The distinct AE (adverse event) profile may be used to council patients and tailor therapy to individual needs.”
In the randomized study with a median 12-month follow up of previously untreated patients with a median age of 71 years, the incidence of grade 4 neutropenia and neutropenic fever were 56% and 10% for 39 patients given doxorubicin and 0% and 0% for 81 patients given pazopanib, respectively. Overall survival was 14.3 months and 12.3 months, a nonsignificant difference. The most frequent adverse events for doxorubicin were fatigue (64.9%), alopecia (56.8%) and nausea (48.6%), and for pazopanib they were fatigue (58%), nausea (43.2%) and diarrhea (43.2%). Similar outcomes were reported for global EORTC QLQ-C30 measures.
EPAZ included patients aged 60 years and older (median 71 years) with no prior systemic treatment for soft tissue sarcoma, progressive disease, ECOG 0-2, and adequate organ function. After 1:2 randomization, patients received either doxorubicin 75 mg/m2 every 3 weeks for a total of 6 cycles or oral pazopanib 800 mg/day given continuously. ECOG 2 and liposarcoma histology were used for stratification.
Dr. Grunwald and several of his co-authors disclosed financial relationships with various drug companies including Novartis, the maker of pazopanib (Votrient). Clinical trial information: NCT01861951
SOURCE: Grunwald V et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11506.
FROM ASCO 2018
ENLIVEN: Pexidartinib improves symptoms, function in patients with advanced tenosynovial giant cell tumors
Pexidartinib significantly improved overall response rates and functioning in patients with advanced tenosynovial giant cell tumors (TGCT), based on the final results of the ENLIVEN study, presented at the annual meeting of the American Society of Clinical Oncology in Chicago.
“Pexidartinib, a novel CSF1 receptor inhibitor, may offer a relevant treatment option for patients with TGCT, which is associated with severe morbidity or functional limitations, and for which surgery is not recommended,” said William Tap, MD, of Memorial Sloan Kettering Cancer Center, New York.
Compared with placebo in patients with advanced, symptomatic TGCT, pexidartinib significantly improved overall response rates; RECIST was 39% with pexidartinib and 0% with placebo. Tumor volume score improvement was 56% with pexidartinib and 0% with placebo. Both results were significant at P less than 0.0001.
“Importantly, these responses correlated with improved patient symptoms and function,” Dr. Tap said. “Pexidartinib was generally well tolerated with serious, nonfatal liver toxicity with increased bilirubin in 4% of patients.” The majority of other adverse events with pexidartinib (hair color changes, vomiting, fatigue, dysgeusia, and periorbital edema) were less than grade 3.
The primary treatment for these patients is surgery; there are currently no approved systemic therapies for advanced tenosynovial giant cell tumor. In previous studies by others, imatinib, evaluated in 27 patients, was associated with a 19% overall response rate (ORR). Nilotinib, evaluated in 51 patients, was associated with a 0% ORR at week 12.
ENLIVEN is a double-blind, randomized, placebo-controlled international, phase 3 study whose participants had histologically confirmed, advanced, symptomatic TGCT of greater than 2 cm. Several had previous surgeries, but further surgical resection would have been associated with the potential for worsening functional limitations or severe morbidity.
In ENLIVEN, 61 patients were randomized to pexidartinib and 59 to placebo. All had recurrent or inoperable TGCT. Patients received placebo or pexidartinib 1000 mg/day (split, BID for 2 weeks) then 800 mg/day (split BID for 22 weeks).
Nine patients in the active treatment group and 11 in the placebo group discontinued therapy. Eight patients discontinued pexidartinib due to hepatic adverse events; all serious hepatic events appeared in the first 2 months of treatment.
At 25 weeks, blinded reviews of MRI scans were performed. A partial response was seen in 12 (52%) patients and stable disease was seen in 7 (30%), based on RECIST 1.1.
Also at week 25, pexidartinib-treated patients did better on scores of functional endpoints related to range of motion, PROMIS physical function, stiffness, and BPI worst pain response. Based on functional endpoints, 9 of 61 (15%) had a complete response and 15 (25%) had a partial response, for an overall response rate of 24 (39%); P less than 0.0001.
None of the 59 patients in the placebo group had a response.
Tumor volume scores at week 25 were complete in 3 (5%) and partial in 31 (51%); overall response rate was 34 (56%); P less than 0.0001. Disease was stable in 14 (23%), progressive in 1 (2%), and not evaluable in 12 (20%). There were no complete or partial responses in the placebo group; disease was stable in 45 (76%), progressive in 2 (3%), and not evaluable in 12 (20%).
Dr. Tap disclosed consulting or advisory roles with Daiichi Sankyo, the maker of pexidartinib; as well as Adaptimmune; Blueprint Medicines; Eisai; EMD Serono; Immune Design; Janssen; Lilly; Loxo; Novartis; Plexxikon; TRACON Pharma. Clinical trial information: NCT02371369.
SOURCE: Tap W et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11502.
Pexidartinib significantly improved overall response rates and functioning in patients with advanced tenosynovial giant cell tumors (TGCT), based on the final results of the ENLIVEN study, presented at the annual meeting of the American Society of Clinical Oncology in Chicago.
“Pexidartinib, a novel CSF1 receptor inhibitor, may offer a relevant treatment option for patients with TGCT, which is associated with severe morbidity or functional limitations, and for which surgery is not recommended,” said William Tap, MD, of Memorial Sloan Kettering Cancer Center, New York.
Compared with placebo in patients with advanced, symptomatic TGCT, pexidartinib significantly improved overall response rates; RECIST was 39% with pexidartinib and 0% with placebo. Tumor volume score improvement was 56% with pexidartinib and 0% with placebo. Both results were significant at P less than 0.0001.
“Importantly, these responses correlated with improved patient symptoms and function,” Dr. Tap said. “Pexidartinib was generally well tolerated with serious, nonfatal liver toxicity with increased bilirubin in 4% of patients.” The majority of other adverse events with pexidartinib (hair color changes, vomiting, fatigue, dysgeusia, and periorbital edema) were less than grade 3.
The primary treatment for these patients is surgery; there are currently no approved systemic therapies for advanced tenosynovial giant cell tumor. In previous studies by others, imatinib, evaluated in 27 patients, was associated with a 19% overall response rate (ORR). Nilotinib, evaluated in 51 patients, was associated with a 0% ORR at week 12.
ENLIVEN is a double-blind, randomized, placebo-controlled international, phase 3 study whose participants had histologically confirmed, advanced, symptomatic TGCT of greater than 2 cm. Several had previous surgeries, but further surgical resection would have been associated with the potential for worsening functional limitations or severe morbidity.
In ENLIVEN, 61 patients were randomized to pexidartinib and 59 to placebo. All had recurrent or inoperable TGCT. Patients received placebo or pexidartinib 1000 mg/day (split, BID for 2 weeks) then 800 mg/day (split BID for 22 weeks).
Nine patients in the active treatment group and 11 in the placebo group discontinued therapy. Eight patients discontinued pexidartinib due to hepatic adverse events; all serious hepatic events appeared in the first 2 months of treatment.
At 25 weeks, blinded reviews of MRI scans were performed. A partial response was seen in 12 (52%) patients and stable disease was seen in 7 (30%), based on RECIST 1.1.
Also at week 25, pexidartinib-treated patients did better on scores of functional endpoints related to range of motion, PROMIS physical function, stiffness, and BPI worst pain response. Based on functional endpoints, 9 of 61 (15%) had a complete response and 15 (25%) had a partial response, for an overall response rate of 24 (39%); P less than 0.0001.
None of the 59 patients in the placebo group had a response.
Tumor volume scores at week 25 were complete in 3 (5%) and partial in 31 (51%); overall response rate was 34 (56%); P less than 0.0001. Disease was stable in 14 (23%), progressive in 1 (2%), and not evaluable in 12 (20%). There were no complete or partial responses in the placebo group; disease was stable in 45 (76%), progressive in 2 (3%), and not evaluable in 12 (20%).
Dr. Tap disclosed consulting or advisory roles with Daiichi Sankyo, the maker of pexidartinib; as well as Adaptimmune; Blueprint Medicines; Eisai; EMD Serono; Immune Design; Janssen; Lilly; Loxo; Novartis; Plexxikon; TRACON Pharma. Clinical trial information: NCT02371369.
SOURCE: Tap W et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11502.
Pexidartinib significantly improved overall response rates and functioning in patients with advanced tenosynovial giant cell tumors (TGCT), based on the final results of the ENLIVEN study, presented at the annual meeting of the American Society of Clinical Oncology in Chicago.
“Pexidartinib, a novel CSF1 receptor inhibitor, may offer a relevant treatment option for patients with TGCT, which is associated with severe morbidity or functional limitations, and for which surgery is not recommended,” said William Tap, MD, of Memorial Sloan Kettering Cancer Center, New York.
Compared with placebo in patients with advanced, symptomatic TGCT, pexidartinib significantly improved overall response rates; RECIST was 39% with pexidartinib and 0% with placebo. Tumor volume score improvement was 56% with pexidartinib and 0% with placebo. Both results were significant at P less than 0.0001.
“Importantly, these responses correlated with improved patient symptoms and function,” Dr. Tap said. “Pexidartinib was generally well tolerated with serious, nonfatal liver toxicity with increased bilirubin in 4% of patients.” The majority of other adverse events with pexidartinib (hair color changes, vomiting, fatigue, dysgeusia, and periorbital edema) were less than grade 3.
The primary treatment for these patients is surgery; there are currently no approved systemic therapies for advanced tenosynovial giant cell tumor. In previous studies by others, imatinib, evaluated in 27 patients, was associated with a 19% overall response rate (ORR). Nilotinib, evaluated in 51 patients, was associated with a 0% ORR at week 12.
ENLIVEN is a double-blind, randomized, placebo-controlled international, phase 3 study whose participants had histologically confirmed, advanced, symptomatic TGCT of greater than 2 cm. Several had previous surgeries, but further surgical resection would have been associated with the potential for worsening functional limitations or severe morbidity.
In ENLIVEN, 61 patients were randomized to pexidartinib and 59 to placebo. All had recurrent or inoperable TGCT. Patients received placebo or pexidartinib 1000 mg/day (split, BID for 2 weeks) then 800 mg/day (split BID for 22 weeks).
Nine patients in the active treatment group and 11 in the placebo group discontinued therapy. Eight patients discontinued pexidartinib due to hepatic adverse events; all serious hepatic events appeared in the first 2 months of treatment.
At 25 weeks, blinded reviews of MRI scans were performed. A partial response was seen in 12 (52%) patients and stable disease was seen in 7 (30%), based on RECIST 1.1.
Also at week 25, pexidartinib-treated patients did better on scores of functional endpoints related to range of motion, PROMIS physical function, stiffness, and BPI worst pain response. Based on functional endpoints, 9 of 61 (15%) had a complete response and 15 (25%) had a partial response, for an overall response rate of 24 (39%); P less than 0.0001.
None of the 59 patients in the placebo group had a response.
Tumor volume scores at week 25 were complete in 3 (5%) and partial in 31 (51%); overall response rate was 34 (56%); P less than 0.0001. Disease was stable in 14 (23%), progressive in 1 (2%), and not evaluable in 12 (20%). There were no complete or partial responses in the placebo group; disease was stable in 45 (76%), progressive in 2 (3%), and not evaluable in 12 (20%).
Dr. Tap disclosed consulting or advisory roles with Daiichi Sankyo, the maker of pexidartinib; as well as Adaptimmune; Blueprint Medicines; Eisai; EMD Serono; Immune Design; Janssen; Lilly; Loxo; Novartis; Plexxikon; TRACON Pharma. Clinical trial information: NCT02371369.
SOURCE: Tap W et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11502.
FROM ASCO 2018
Youth with rhabdomyosarcoma see better survival with maintenance chemo
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.