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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.
Maintenance chemo boosts survival for youth with high-risk rhabdomyosarcoma
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Maintenance chemotherapy is life-prolonging for youth with high-risk rhabdomyosarcoma, finds a trial of 371 patients aged 0 to 21 years who had completed standard intensive therapy.
The 5-year rate of overall survival was 86.5% for those who received maintenance therapy with the combination of low-dose intravenous vinorelbine and oral cyclophosphamide, compared with 73.7% for those who did not, translating to a near halving of the risk of death (hazard ratio, 0.52; P = .0111). The regimen was well tolerated.
In an interview at the annual meeting of the American Society of Clinical Oncology, lead study author Gianni Bisogno, MD, PhD, discussed the risk-benefit profile of maintenance chemotherapy and the practice-changing nature of the new data. Dr. Bisogno, a professor at the University Hospital of Padova in Italy and chair of the European Paediatric Soft tissue Sarcoma Study Group, also described plans for a new trial that will explore alternate maintenance schedules and collaboration with colleagues in North America to further improve pediatric rhabdomyosarcoma outcomes.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Maintenance chemotherapy is life-prolonging for youth with high-risk rhabdomyosarcoma, finds a trial of 371 patients aged 0 to 21 years who had completed standard intensive therapy.
The 5-year rate of overall survival was 86.5% for those who received maintenance therapy with the combination of low-dose intravenous vinorelbine and oral cyclophosphamide, compared with 73.7% for those who did not, translating to a near halving of the risk of death (hazard ratio, 0.52; P = .0111). The regimen was well tolerated.
In an interview at the annual meeting of the American Society of Clinical Oncology, lead study author Gianni Bisogno, MD, PhD, discussed the risk-benefit profile of maintenance chemotherapy and the practice-changing nature of the new data. Dr. Bisogno, a professor at the University Hospital of Padova in Italy and chair of the European Paediatric Soft tissue Sarcoma Study Group, also described plans for a new trial that will explore alternate maintenance schedules and collaboration with colleagues in North America to further improve pediatric rhabdomyosarcoma outcomes.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Maintenance chemotherapy is life-prolonging for youth with high-risk rhabdomyosarcoma, finds a trial of 371 patients aged 0 to 21 years who had completed standard intensive therapy.
The 5-year rate of overall survival was 86.5% for those who received maintenance therapy with the combination of low-dose intravenous vinorelbine and oral cyclophosphamide, compared with 73.7% for those who did not, translating to a near halving of the risk of death (hazard ratio, 0.52; P = .0111). The regimen was well tolerated.
In an interview at the annual meeting of the American Society of Clinical Oncology, lead study author Gianni Bisogno, MD, PhD, discussed the risk-benefit profile of maintenance chemotherapy and the practice-changing nature of the new data. Dr. Bisogno, a professor at the University Hospital of Padova in Italy and chair of the European Paediatric Soft tissue Sarcoma Study Group, also described plans for a new trial that will explore alternate maintenance schedules and collaboration with colleagues in North America to further improve pediatric rhabdomyosarcoma outcomes.
REPORTING FROM ASCO 2018
cfDNA reveals targetable mutations in pediatric neuroblastoma, sarcoma
PITTSBURGH – Genetic analysis of circulating free DNA (cfDNA) from pediatric solid tumors can noninvasively identify somatic mutations and copy number alterations that could be used to identify therapeutic targets, investigators reported.
An analysis of tumor specimens and plasma samples from children with neuroblastoma, osteosarcoma, and Wilms tumor revealed in cfDNA both somatic mutations and copy number alterations that had already been detected in the solid tumors, and new, potentially targetable mutations, reported Prachi Kothari, DO, and her colleagues from Memorial Sloan Kettering Cancer Center in New York.
“Circulating free DNA is much less invasive than a tumor biopsy, and you can do it throughout the patient’s entire timeline of treatment, so you get real-time information or after they relapse to see what’s going on if you’re not able to get a tumor biopsy,” Dr. Kothari said at annual meeting of the American Society of Pediatric Hematology/Oncology.
So-called “liquid biopsy” using cfDNA has been used for molecular profiling of adults malignancies, but there are few data on its use in pediatric tumors, Dr. Kothari said.
To see whether the technique could provide useful clinical information for the management of pediatric tumors, the investigators examined tumor samples taken at diagnosis or at the time of disease progression from 15 patients with neuroblastoma, 10 with osteosarcoma, and 5 with Wilms tumor. They analyzed the tumor samples using targeted next-generation sequencing (NGS), and cfDNA using three different genomic analysis techniques, including NGS, MSK-IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets), and shallow whole genome sequencing.
For each of the tumor types studies, cfDNA analysis with the MSK-IMPACT platform identified key drivers of malignancy, including MYCN, ALK, and ATRX in neuroblastoma; CDKN2A and MDM2 in osteosarcoma; and DICER1 and AMER1 in Wilms tumor.
The cfDNA samples also revealed somatic mutations and copy number alterations previously reported in the tumors of 8 of the 15 patients with neuroblastoma, as well as potentially targetable new mutations in 6 of the 15 patients, including NRAS, MLL2, ARID1B, and IDH2.
For example, in one patient with stage 4 MYCN-amplified neuroblastoma, both tumor analysis and cfDNA revealed MYCN amplification, but cfDNA also show multiple new mutations, including a targetable NRAS mutation, secondary to clonal mutation.
In 5 of the 10 patients with osteosarcoma, cfDNA detected mutations that had been seen in the tumor samples, including mutations in ATRX and NOTCH3, and copy number alterations such as CDK4 amplification,
Of the five patients with Wilms tumors, cfDNA analysis was performed on two samples, one of which showed the same mutation as the tumor. Additionally, for the three patients without tumor analysis, cfDNA showed recurrent driver mutations such as AMER1 and DICER1.
The investigators have used the data from this study to create a genome-wide z score derived from shallow whole genome sequencing profiles and cfDNA, and found that a high genomewide z score, compared with a low score was significantly associated a more than four-fold greater risk for worse survival (hazard ratio, 4.42; P = .049).
“Establishing a platform using cfDNA to identify molecular profiles of these tumors can serve as a powerful tool for guiding treatment and monitoring response to treatment,” the investigators concluded.
The study was supported by Cycle for Survival and the Kristen Ann Carr Fund. The investigators reported having no conflicts of interest.
SOURCE: Kothari P et al. ASPHO 2018. Abstract #809.
PITTSBURGH – Genetic analysis of circulating free DNA (cfDNA) from pediatric solid tumors can noninvasively identify somatic mutations and copy number alterations that could be used to identify therapeutic targets, investigators reported.
An analysis of tumor specimens and plasma samples from children with neuroblastoma, osteosarcoma, and Wilms tumor revealed in cfDNA both somatic mutations and copy number alterations that had already been detected in the solid tumors, and new, potentially targetable mutations, reported Prachi Kothari, DO, and her colleagues from Memorial Sloan Kettering Cancer Center in New York.
“Circulating free DNA is much less invasive than a tumor biopsy, and you can do it throughout the patient’s entire timeline of treatment, so you get real-time information or after they relapse to see what’s going on if you’re not able to get a tumor biopsy,” Dr. Kothari said at annual meeting of the American Society of Pediatric Hematology/Oncology.
So-called “liquid biopsy” using cfDNA has been used for molecular profiling of adults malignancies, but there are few data on its use in pediatric tumors, Dr. Kothari said.
To see whether the technique could provide useful clinical information for the management of pediatric tumors, the investigators examined tumor samples taken at diagnosis or at the time of disease progression from 15 patients with neuroblastoma, 10 with osteosarcoma, and 5 with Wilms tumor. They analyzed the tumor samples using targeted next-generation sequencing (NGS), and cfDNA using three different genomic analysis techniques, including NGS, MSK-IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets), and shallow whole genome sequencing.
For each of the tumor types studies, cfDNA analysis with the MSK-IMPACT platform identified key drivers of malignancy, including MYCN, ALK, and ATRX in neuroblastoma; CDKN2A and MDM2 in osteosarcoma; and DICER1 and AMER1 in Wilms tumor.
The cfDNA samples also revealed somatic mutations and copy number alterations previously reported in the tumors of 8 of the 15 patients with neuroblastoma, as well as potentially targetable new mutations in 6 of the 15 patients, including NRAS, MLL2, ARID1B, and IDH2.
For example, in one patient with stage 4 MYCN-amplified neuroblastoma, both tumor analysis and cfDNA revealed MYCN amplification, but cfDNA also show multiple new mutations, including a targetable NRAS mutation, secondary to clonal mutation.
In 5 of the 10 patients with osteosarcoma, cfDNA detected mutations that had been seen in the tumor samples, including mutations in ATRX and NOTCH3, and copy number alterations such as CDK4 amplification,
Of the five patients with Wilms tumors, cfDNA analysis was performed on two samples, one of which showed the same mutation as the tumor. Additionally, for the three patients without tumor analysis, cfDNA showed recurrent driver mutations such as AMER1 and DICER1.
The investigators have used the data from this study to create a genome-wide z score derived from shallow whole genome sequencing profiles and cfDNA, and found that a high genomewide z score, compared with a low score was significantly associated a more than four-fold greater risk for worse survival (hazard ratio, 4.42; P = .049).
“Establishing a platform using cfDNA to identify molecular profiles of these tumors can serve as a powerful tool for guiding treatment and monitoring response to treatment,” the investigators concluded.
The study was supported by Cycle for Survival and the Kristen Ann Carr Fund. The investigators reported having no conflicts of interest.
SOURCE: Kothari P et al. ASPHO 2018. Abstract #809.
PITTSBURGH – Genetic analysis of circulating free DNA (cfDNA) from pediatric solid tumors can noninvasively identify somatic mutations and copy number alterations that could be used to identify therapeutic targets, investigators reported.
An analysis of tumor specimens and plasma samples from children with neuroblastoma, osteosarcoma, and Wilms tumor revealed in cfDNA both somatic mutations and copy number alterations that had already been detected in the solid tumors, and new, potentially targetable mutations, reported Prachi Kothari, DO, and her colleagues from Memorial Sloan Kettering Cancer Center in New York.
“Circulating free DNA is much less invasive than a tumor biopsy, and you can do it throughout the patient’s entire timeline of treatment, so you get real-time information or after they relapse to see what’s going on if you’re not able to get a tumor biopsy,” Dr. Kothari said at annual meeting of the American Society of Pediatric Hematology/Oncology.
So-called “liquid biopsy” using cfDNA has been used for molecular profiling of adults malignancies, but there are few data on its use in pediatric tumors, Dr. Kothari said.
To see whether the technique could provide useful clinical information for the management of pediatric tumors, the investigators examined tumor samples taken at diagnosis or at the time of disease progression from 15 patients with neuroblastoma, 10 with osteosarcoma, and 5 with Wilms tumor. They analyzed the tumor samples using targeted next-generation sequencing (NGS), and cfDNA using three different genomic analysis techniques, including NGS, MSK-IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets), and shallow whole genome sequencing.
For each of the tumor types studies, cfDNA analysis with the MSK-IMPACT platform identified key drivers of malignancy, including MYCN, ALK, and ATRX in neuroblastoma; CDKN2A and MDM2 in osteosarcoma; and DICER1 and AMER1 in Wilms tumor.
The cfDNA samples also revealed somatic mutations and copy number alterations previously reported in the tumors of 8 of the 15 patients with neuroblastoma, as well as potentially targetable new mutations in 6 of the 15 patients, including NRAS, MLL2, ARID1B, and IDH2.
For example, in one patient with stage 4 MYCN-amplified neuroblastoma, both tumor analysis and cfDNA revealed MYCN amplification, but cfDNA also show multiple new mutations, including a targetable NRAS mutation, secondary to clonal mutation.
In 5 of the 10 patients with osteosarcoma, cfDNA detected mutations that had been seen in the tumor samples, including mutations in ATRX and NOTCH3, and copy number alterations such as CDK4 amplification,
Of the five patients with Wilms tumors, cfDNA analysis was performed on two samples, one of which showed the same mutation as the tumor. Additionally, for the three patients without tumor analysis, cfDNA showed recurrent driver mutations such as AMER1 and DICER1.
The investigators have used the data from this study to create a genome-wide z score derived from shallow whole genome sequencing profiles and cfDNA, and found that a high genomewide z score, compared with a low score was significantly associated a more than four-fold greater risk for worse survival (hazard ratio, 4.42; P = .049).
“Establishing a platform using cfDNA to identify molecular profiles of these tumors can serve as a powerful tool for guiding treatment and monitoring response to treatment,” the investigators concluded.
The study was supported by Cycle for Survival and the Kristen Ann Carr Fund. The investigators reported having no conflicts of interest.
SOURCE: Kothari P et al. ASPHO 2018. Abstract #809.
REPORTING FROM ASPHO 2018
Key clinical point: Circulating free DNA analysis is a noninvasive method for detecting potential therapeutic targets.
Major finding: cfDNA revealed potentially targetable new mutations in 6 of 15 patients with neuroblastoma.
Study details: Retrospective analysis of tumor and plasma samples in 30 patients with neuroblastoma, osteosarcoma, or Wilms tumor.
Disclosures: The study was supported by Cycle for Survival and the Kristen Ann Carr Fund. The investigators reported having no conflicts of interest.
Source: Kothari P et al. ASPHO 2018. Abstract #809.
Multiple solid tumors targeted by concept CAR T
PITTSBURGH – Call it the CAR of the future – an investigational chimeric antigen receptor–T cell construct targeted against an antigen highly expressed on pediatric solid tumors has shown promising efficacy in preclinical studies.
Investigators found that the antigen, labeled B7-H3, was expressed on 84% of microarrays of pediatric solid tumors. More importantly, a single dose of CAR targeted to B7-H3 caused complete regression of osteosarcoma and Ewing sarcoma xenografts and improved survival over an untransduced, CD19-targeted CAR in mice, Robbie Majzner, MD, reported at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Dr. Majzner was the recipient of an ASPHO young investigator award for his team’s research into developing a CAR T that could be as effective against solid tumors as other CAR Ts have been against hematologic malignancies such as acute lymphoblastic leukemia.
Solid tumors are more challenging to target than leukemias or lymphomas because of the small number of antigens expressed on most pediatric tumors, he said.
“Over 95% of tumors have a very low rate of mutations, which means that they have very few neoantigens which the immune system can recognize in order to attack,” he said.
In the Children’s Oncology Group ADVL1412 trial, single-agent immunotherapy with the anti–programmed death protein 1 (PD-1) inhibitor nivolumab (Opdivo) showed no evidence of efficacy against either Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, or measurable neuroblastoma. PD–ligand 1 was found to be expressed in only a few of the 43 tumors studied, suggesting that checkpoint inhibitor therapy is unlikely to work in these solid tumors, he said.
In contrast, B7-H3 is highly expressed on many different pediatric solid tumors, including rhabdomyosarcoma (95% of tumors stained), Ewing sarcoma (89%), Wilms tumor (100%), neuroblastoma (82%), ganglioneuroblastoma and ganglioneuroma (53%), medulloblastoma (96%), glioblastoma multiforme (84%), and diffuse intrinsic pontine glioma (100%).
To see whether CAR T therapy might have better efficacy than checkpoint inhibitors in this population, the investigators created a B7-H3 CAR using the B7-H3 tumor–specific monoclonal antibody MGA271, which has been shown to be safe in both adults and children in early clinical trials.
In human tumor xenograft models of osteosarcoma, all mice who received a single dose of the B7-H3 CAR survived at least 70 days after tumor engraftment, whereas all control mice, who received the CD19 CAR, died by day 60 (P = .0067). Similarly, in a model of Ewing sarcoma, all mice treated with B7-H3 survived at least 100 days, whereas all controls were dead by day 50 (P = .0015).
The B7-H3 construct also showed good activity against a model of medulloblastoma, showing that it was capable of crossing the blood-brain barrier.
Since B7-H3 has been reported to be expressed on both myeloid and lymphoid leukemia cells, the investigators also tested the CAR against a murine model of leukemia generated by injection of K562, a well-characterized line of myeloid leukemia cells.
“While we found some increase in survival in the mice that received the B7-H3 CAR T cells, compared to mice that received untransduced CAR T cells, this clearly is not as effective as in our solid tumor models,” Dr. Majzner said.
Going back to the cell line, they discovered that expression of B7-H3 was considerably lower in the K562 cells than in either the osteosarcoma or medulloblastoma cell lines used in their other models.
They found that both in vitro and in vivo, high levels of B7-H3 expression were necessary to provoke the immune system into releasing cytokines necessary for an adequate antitumor response.
The investigators are currently planning clinical trials using the B7-H3 CAR T-cell construct in patients with solid tumors.
The work is supported by the Sarcoma Alliance for Research through Collaboration, the St. Baldrick’s Foundation, and Stand Up to Cancer. Dr. Majzner reported having no financial disclosures.
SOURCE: Majzner RG et al. ASPHO 2018, Abstract #PS2003.
PITTSBURGH – Call it the CAR of the future – an investigational chimeric antigen receptor–T cell construct targeted against an antigen highly expressed on pediatric solid tumors has shown promising efficacy in preclinical studies.
Investigators found that the antigen, labeled B7-H3, was expressed on 84% of microarrays of pediatric solid tumors. More importantly, a single dose of CAR targeted to B7-H3 caused complete regression of osteosarcoma and Ewing sarcoma xenografts and improved survival over an untransduced, CD19-targeted CAR in mice, Robbie Majzner, MD, reported at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Dr. Majzner was the recipient of an ASPHO young investigator award for his team’s research into developing a CAR T that could be as effective against solid tumors as other CAR Ts have been against hematologic malignancies such as acute lymphoblastic leukemia.
Solid tumors are more challenging to target than leukemias or lymphomas because of the small number of antigens expressed on most pediatric tumors, he said.
“Over 95% of tumors have a very low rate of mutations, which means that they have very few neoantigens which the immune system can recognize in order to attack,” he said.
In the Children’s Oncology Group ADVL1412 trial, single-agent immunotherapy with the anti–programmed death protein 1 (PD-1) inhibitor nivolumab (Opdivo) showed no evidence of efficacy against either Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, or measurable neuroblastoma. PD–ligand 1 was found to be expressed in only a few of the 43 tumors studied, suggesting that checkpoint inhibitor therapy is unlikely to work in these solid tumors, he said.
In contrast, B7-H3 is highly expressed on many different pediatric solid tumors, including rhabdomyosarcoma (95% of tumors stained), Ewing sarcoma (89%), Wilms tumor (100%), neuroblastoma (82%), ganglioneuroblastoma and ganglioneuroma (53%), medulloblastoma (96%), glioblastoma multiforme (84%), and diffuse intrinsic pontine glioma (100%).
To see whether CAR T therapy might have better efficacy than checkpoint inhibitors in this population, the investigators created a B7-H3 CAR using the B7-H3 tumor–specific monoclonal antibody MGA271, which has been shown to be safe in both adults and children in early clinical trials.
In human tumor xenograft models of osteosarcoma, all mice who received a single dose of the B7-H3 CAR survived at least 70 days after tumor engraftment, whereas all control mice, who received the CD19 CAR, died by day 60 (P = .0067). Similarly, in a model of Ewing sarcoma, all mice treated with B7-H3 survived at least 100 days, whereas all controls were dead by day 50 (P = .0015).
The B7-H3 construct also showed good activity against a model of medulloblastoma, showing that it was capable of crossing the blood-brain barrier.
Since B7-H3 has been reported to be expressed on both myeloid and lymphoid leukemia cells, the investigators also tested the CAR against a murine model of leukemia generated by injection of K562, a well-characterized line of myeloid leukemia cells.
“While we found some increase in survival in the mice that received the B7-H3 CAR T cells, compared to mice that received untransduced CAR T cells, this clearly is not as effective as in our solid tumor models,” Dr. Majzner said.
Going back to the cell line, they discovered that expression of B7-H3 was considerably lower in the K562 cells than in either the osteosarcoma or medulloblastoma cell lines used in their other models.
They found that both in vitro and in vivo, high levels of B7-H3 expression were necessary to provoke the immune system into releasing cytokines necessary for an adequate antitumor response.
The investigators are currently planning clinical trials using the B7-H3 CAR T-cell construct in patients with solid tumors.
The work is supported by the Sarcoma Alliance for Research through Collaboration, the St. Baldrick’s Foundation, and Stand Up to Cancer. Dr. Majzner reported having no financial disclosures.
SOURCE: Majzner RG et al. ASPHO 2018, Abstract #PS2003.
PITTSBURGH – Call it the CAR of the future – an investigational chimeric antigen receptor–T cell construct targeted against an antigen highly expressed on pediatric solid tumors has shown promising efficacy in preclinical studies.
Investigators found that the antigen, labeled B7-H3, was expressed on 84% of microarrays of pediatric solid tumors. More importantly, a single dose of CAR targeted to B7-H3 caused complete regression of osteosarcoma and Ewing sarcoma xenografts and improved survival over an untransduced, CD19-targeted CAR in mice, Robbie Majzner, MD, reported at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Dr. Majzner was the recipient of an ASPHO young investigator award for his team’s research into developing a CAR T that could be as effective against solid tumors as other CAR Ts have been against hematologic malignancies such as acute lymphoblastic leukemia.
Solid tumors are more challenging to target than leukemias or lymphomas because of the small number of antigens expressed on most pediatric tumors, he said.
“Over 95% of tumors have a very low rate of mutations, which means that they have very few neoantigens which the immune system can recognize in order to attack,” he said.
In the Children’s Oncology Group ADVL1412 trial, single-agent immunotherapy with the anti–programmed death protein 1 (PD-1) inhibitor nivolumab (Opdivo) showed no evidence of efficacy against either Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, or measurable neuroblastoma. PD–ligand 1 was found to be expressed in only a few of the 43 tumors studied, suggesting that checkpoint inhibitor therapy is unlikely to work in these solid tumors, he said.
In contrast, B7-H3 is highly expressed on many different pediatric solid tumors, including rhabdomyosarcoma (95% of tumors stained), Ewing sarcoma (89%), Wilms tumor (100%), neuroblastoma (82%), ganglioneuroblastoma and ganglioneuroma (53%), medulloblastoma (96%), glioblastoma multiforme (84%), and diffuse intrinsic pontine glioma (100%).
To see whether CAR T therapy might have better efficacy than checkpoint inhibitors in this population, the investigators created a B7-H3 CAR using the B7-H3 tumor–specific monoclonal antibody MGA271, which has been shown to be safe in both adults and children in early clinical trials.
In human tumor xenograft models of osteosarcoma, all mice who received a single dose of the B7-H3 CAR survived at least 70 days after tumor engraftment, whereas all control mice, who received the CD19 CAR, died by day 60 (P = .0067). Similarly, in a model of Ewing sarcoma, all mice treated with B7-H3 survived at least 100 days, whereas all controls were dead by day 50 (P = .0015).
The B7-H3 construct also showed good activity against a model of medulloblastoma, showing that it was capable of crossing the blood-brain barrier.
Since B7-H3 has been reported to be expressed on both myeloid and lymphoid leukemia cells, the investigators also tested the CAR against a murine model of leukemia generated by injection of K562, a well-characterized line of myeloid leukemia cells.
“While we found some increase in survival in the mice that received the B7-H3 CAR T cells, compared to mice that received untransduced CAR T cells, this clearly is not as effective as in our solid tumor models,” Dr. Majzner said.
Going back to the cell line, they discovered that expression of B7-H3 was considerably lower in the K562 cells than in either the osteosarcoma or medulloblastoma cell lines used in their other models.
They found that both in vitro and in vivo, high levels of B7-H3 expression were necessary to provoke the immune system into releasing cytokines necessary for an adequate antitumor response.
The investigators are currently planning clinical trials using the B7-H3 CAR T-cell construct in patients with solid tumors.
The work is supported by the Sarcoma Alliance for Research through Collaboration, the St. Baldrick’s Foundation, and Stand Up to Cancer. Dr. Majzner reported having no financial disclosures.
SOURCE: Majzner RG et al. ASPHO 2018, Abstract #PS2003.
REPORTING FROM ASPHO 2018
Key clinical point:
Major finding: A single dose of the B7-H3 CAR caused complete regression of osteosarcoma and Ewing sarcoma xenografts and extended survival in mice.
Study details: Preclinical research.
Disclosures: The work is supported by the Sarcoma Alliance for Research through Collaboration, St. Baldrick’s Foundation, and Stand Up to Cancer. Dr. Majzner reported having no financial disclosures.
Source: Majzner RG et al. ASPHO 2018, Abstract #PS2003.
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