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FDA announces plan for biosimilar innovation and competition
Some of the actions include tools to enhance public information about the FDA’s evaluation of biosimilars, including more information about approved biological products in the Purple Book; exploring the potential for entering into new data sharing agreements with foreign regulators to facilitate the increased use of non–U.S.-licensed comparator products in certain studies to support a biosimilar application; releasing a series of videos that explain key concepts about biosimilar and interchangeable products; and requesting information from the public on additional policy steps the FDA should consider for enhancing the biosimilar program.
The FDA’s Biosimilar Action Plan is available here.
Some of the actions include tools to enhance public information about the FDA’s evaluation of biosimilars, including more information about approved biological products in the Purple Book; exploring the potential for entering into new data sharing agreements with foreign regulators to facilitate the increased use of non–U.S.-licensed comparator products in certain studies to support a biosimilar application; releasing a series of videos that explain key concepts about biosimilar and interchangeable products; and requesting information from the public on additional policy steps the FDA should consider for enhancing the biosimilar program.
The FDA’s Biosimilar Action Plan is available here.
Some of the actions include tools to enhance public information about the FDA’s evaluation of biosimilars, including more information about approved biological products in the Purple Book; exploring the potential for entering into new data sharing agreements with foreign regulators to facilitate the increased use of non–U.S.-licensed comparator products in certain studies to support a biosimilar application; releasing a series of videos that explain key concepts about biosimilar and interchangeable products; and requesting information from the public on additional policy steps the FDA should consider for enhancing the biosimilar program.
The FDA’s Biosimilar Action Plan is available here.
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
FDA approves Doptelet for liver disease patients undergoing procedures
Doptelet (avatrombopag) is the first drug to be approved by the Food and Drug Administration for thrombocytopenia in adults with chronic liver disease who are scheduled to undergo a medical or dental procedure, the FDA announced in a statement.
“Patients with chronic liver disease who have low platelet counts and require a procedure are at increased risk of bleeding,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Doptelet was demonstrated to safely increase the platelet count. This drug may decrease or eliminate the need for platelet transfusions, which are associated with risk of infection and other adverse reactions.”
The safety and efficacy of two different doses of Doptelet administered orally over 5 days, as compared with placebo, was studied in the ADAPT trials (ADAPT-1 and ADAPT-2) involving 435 patients with chronic liver disease and severe thrombocytopenia who were scheduled to undergo a procedure that would typically require platelet transfusion. At both dose levels of Doptelet, a higher proportion of patients had increased platelet counts and did not require platelet transfusion or any rescue therapy on the day of the procedure and up to 7 days following the procedure as compared with those treated with placebo.
The most common side effects reported by clinical trial participants who received Doptelet were fever, stomach (abdominal) pain, nausea, headache, fatigue and edema in the hands or feet. People with chronic liver disease and people with certain blood clotting conditions may have an increased risk of developing blood clots when taking Doptelet, the FDA said in a press release announcing the approval.
The FDA granted the Doptelet approval to AkaRx.
Doptelet (avatrombopag) is the first drug to be approved by the Food and Drug Administration for thrombocytopenia in adults with chronic liver disease who are scheduled to undergo a medical or dental procedure, the FDA announced in a statement.
“Patients with chronic liver disease who have low platelet counts and require a procedure are at increased risk of bleeding,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Doptelet was demonstrated to safely increase the platelet count. This drug may decrease or eliminate the need for platelet transfusions, which are associated with risk of infection and other adverse reactions.”
The safety and efficacy of two different doses of Doptelet administered orally over 5 days, as compared with placebo, was studied in the ADAPT trials (ADAPT-1 and ADAPT-2) involving 435 patients with chronic liver disease and severe thrombocytopenia who were scheduled to undergo a procedure that would typically require platelet transfusion. At both dose levels of Doptelet, a higher proportion of patients had increased platelet counts and did not require platelet transfusion or any rescue therapy on the day of the procedure and up to 7 days following the procedure as compared with those treated with placebo.
The most common side effects reported by clinical trial participants who received Doptelet were fever, stomach (abdominal) pain, nausea, headache, fatigue and edema in the hands or feet. People with chronic liver disease and people with certain blood clotting conditions may have an increased risk of developing blood clots when taking Doptelet, the FDA said in a press release announcing the approval.
The FDA granted the Doptelet approval to AkaRx.
Doptelet (avatrombopag) is the first drug to be approved by the Food and Drug Administration for thrombocytopenia in adults with chronic liver disease who are scheduled to undergo a medical or dental procedure, the FDA announced in a statement.
“Patients with chronic liver disease who have low platelet counts and require a procedure are at increased risk of bleeding,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Doptelet was demonstrated to safely increase the platelet count. This drug may decrease or eliminate the need for platelet transfusions, which are associated with risk of infection and other adverse reactions.”
The safety and efficacy of two different doses of Doptelet administered orally over 5 days, as compared with placebo, was studied in the ADAPT trials (ADAPT-1 and ADAPT-2) involving 435 patients with chronic liver disease and severe thrombocytopenia who were scheduled to undergo a procedure that would typically require platelet transfusion. At both dose levels of Doptelet, a higher proportion of patients had increased platelet counts and did not require platelet transfusion or any rescue therapy on the day of the procedure and up to 7 days following the procedure as compared with those treated with placebo.
The most common side effects reported by clinical trial participants who received Doptelet were fever, stomach (abdominal) pain, nausea, headache, fatigue and edema in the hands or feet. People with chronic liver disease and people with certain blood clotting conditions may have an increased risk of developing blood clots when taking Doptelet, the FDA said in a press release announcing the approval.
The FDA granted the Doptelet approval to AkaRx.
Sarcoma dominance in uterine carcinosarcomas linked to decreased survival
Sarcoma dominance in uterine carcinosarcomas was associated with decreased survival among women with stages I-IV uterine carcinosarcomas who underwent primary surgery, according to Dr Koji Matsuo, MD, PhD, of the Keck School of Medicine, University of Southern California, Los Angeles, and his colleagues.
The researchers additionally found that adding radiotherapy to chemotherapy may be an effective postoperative strategy for these patients.
Uterine carcinosarcomas are rare, high-grade endometrial cancers that represent 5% of all endometrial cancers. Sarcoma dominance was defined as having more than a 50% sarcoma component in the uterine tumor. In this study, the sarcoma component was grouped as homologous (endometrial stromal sarcoma, leiomyosarcoma, fibrosarcoma, and undifferentiated sarcoma) or heterologous (rhabdomyosarcoma, osteosarcoma, chondrosarcoma, and liposarcoma) types
Among 1,192 cases of uterine carcinosarcomas identified in a secondary analysis of a multicenter retrospective study, 906 cases were available for histopathology slide review. Of those, 889 cases had evaluation for sarcoma dominance. The most common group was homologous sarcoma without sarcoma dominance (39.5%), followed by heterologous sarcoma with sarcoma dominance (21.3%), homologous sarcoma with sarcoma dominance (19.7%) and heterologous sarcoma with sarcoma non-dominance (19.6%), they reported in a study published online in Surgical Oncology https://doi.org/10.1016/j.suronc.2018.05.017
On univariate analysis, sarcoma dominance was associated with decreased progression-free survival (PFS) and cause-specific survival (CSS) in homologous cases (P less than 0.05) but not in heterologous cases. On multivariate models, both homologous and heterologous SD patterns remained independent prognostic factors for decreased PFS (adjusted-hazard ratio [HR] ranges: homologous/dominance 1.35-1.69, and heterologous/dominance 1.47-1.64) and CSS (adjusted-HR ranges: 1.52-1.84 and 1.66-1.81, respectively) compared to homologous/non-dominance (all, P less than 0.05).
In women with stage I-III disease, and tumors with sarcoma dominance, adding radiotherapy to chemotherapy was associated with improved PFS (adjusted-HR: homologous/dominance 0.49, and heterologous/dominance 0.45) and CSS (0.36 and 0.31, respectively) compared to chemotherapy alone (all, P less than 0.05); This association was not observed in women with tumors that lacked sarcoma dominance (all, P greater than 0.05), the researchers said.
Sarcoma dominance in uterine carcinosarcomas was associated with decreased survival among women with stages I-IV uterine carcinosarcomas who underwent primary surgery, according to Dr Koji Matsuo, MD, PhD, of the Keck School of Medicine, University of Southern California, Los Angeles, and his colleagues.
The researchers additionally found that adding radiotherapy to chemotherapy may be an effective postoperative strategy for these patients.
Uterine carcinosarcomas are rare, high-grade endometrial cancers that represent 5% of all endometrial cancers. Sarcoma dominance was defined as having more than a 50% sarcoma component in the uterine tumor. In this study, the sarcoma component was grouped as homologous (endometrial stromal sarcoma, leiomyosarcoma, fibrosarcoma, and undifferentiated sarcoma) or heterologous (rhabdomyosarcoma, osteosarcoma, chondrosarcoma, and liposarcoma) types
Among 1,192 cases of uterine carcinosarcomas identified in a secondary analysis of a multicenter retrospective study, 906 cases were available for histopathology slide review. Of those, 889 cases had evaluation for sarcoma dominance. The most common group was homologous sarcoma without sarcoma dominance (39.5%), followed by heterologous sarcoma with sarcoma dominance (21.3%), homologous sarcoma with sarcoma dominance (19.7%) and heterologous sarcoma with sarcoma non-dominance (19.6%), they reported in a study published online in Surgical Oncology https://doi.org/10.1016/j.suronc.2018.05.017
On univariate analysis, sarcoma dominance was associated with decreased progression-free survival (PFS) and cause-specific survival (CSS) in homologous cases (P less than 0.05) but not in heterologous cases. On multivariate models, both homologous and heterologous SD patterns remained independent prognostic factors for decreased PFS (adjusted-hazard ratio [HR] ranges: homologous/dominance 1.35-1.69, and heterologous/dominance 1.47-1.64) and CSS (adjusted-HR ranges: 1.52-1.84 and 1.66-1.81, respectively) compared to homologous/non-dominance (all, P less than 0.05).
In women with stage I-III disease, and tumors with sarcoma dominance, adding radiotherapy to chemotherapy was associated with improved PFS (adjusted-HR: homologous/dominance 0.49, and heterologous/dominance 0.45) and CSS (0.36 and 0.31, respectively) compared to chemotherapy alone (all, P less than 0.05); This association was not observed in women with tumors that lacked sarcoma dominance (all, P greater than 0.05), the researchers said.
Sarcoma dominance in uterine carcinosarcomas was associated with decreased survival among women with stages I-IV uterine carcinosarcomas who underwent primary surgery, according to Dr Koji Matsuo, MD, PhD, of the Keck School of Medicine, University of Southern California, Los Angeles, and his colleagues.
The researchers additionally found that adding radiotherapy to chemotherapy may be an effective postoperative strategy for these patients.
Uterine carcinosarcomas are rare, high-grade endometrial cancers that represent 5% of all endometrial cancers. Sarcoma dominance was defined as having more than a 50% sarcoma component in the uterine tumor. In this study, the sarcoma component was grouped as homologous (endometrial stromal sarcoma, leiomyosarcoma, fibrosarcoma, and undifferentiated sarcoma) or heterologous (rhabdomyosarcoma, osteosarcoma, chondrosarcoma, and liposarcoma) types
Among 1,192 cases of uterine carcinosarcomas identified in a secondary analysis of a multicenter retrospective study, 906 cases were available for histopathology slide review. Of those, 889 cases had evaluation for sarcoma dominance. The most common group was homologous sarcoma without sarcoma dominance (39.5%), followed by heterologous sarcoma with sarcoma dominance (21.3%), homologous sarcoma with sarcoma dominance (19.7%) and heterologous sarcoma with sarcoma non-dominance (19.6%), they reported in a study published online in Surgical Oncology https://doi.org/10.1016/j.suronc.2018.05.017
On univariate analysis, sarcoma dominance was associated with decreased progression-free survival (PFS) and cause-specific survival (CSS) in homologous cases (P less than 0.05) but not in heterologous cases. On multivariate models, both homologous and heterologous SD patterns remained independent prognostic factors for decreased PFS (adjusted-hazard ratio [HR] ranges: homologous/dominance 1.35-1.69, and heterologous/dominance 1.47-1.64) and CSS (adjusted-HR ranges: 1.52-1.84 and 1.66-1.81, respectively) compared to homologous/non-dominance (all, P less than 0.05).
In women with stage I-III disease, and tumors with sarcoma dominance, adding radiotherapy to chemotherapy was associated with improved PFS (adjusted-HR: homologous/dominance 0.49, and heterologous/dominance 0.45) and CSS (0.36 and 0.31, respectively) compared to chemotherapy alone (all, P less than 0.05); This association was not observed in women with tumors that lacked sarcoma dominance (all, P greater than 0.05), the researchers said.
FROM SURGICAL ONCOLOGY