Sarcoma & GIST

Objectives: Masitinib, a novel, multitargeted, tyrosine kinase inhibitor, is compared with imatinib (Gleevec) in this phase III trial. Investigators ask whether it can improve progression-free survival; overall survival is a secondary outcome measure.

Key entry or exclusion criteria: Patients must have metastatic or locally advanced nonresectable or recurrent postsurgery GIST.

Locations: 43 sites.

Goal: 222 patients.

Study sponsor: AB Science.

Links for more information: clinicaltrials.gov/ct2/show/study/NCT00812240

NIH clinical trials identifier: NCT00812240

Objectives: Masitinib, a novel, multitargeted, tyrosine kinase inhibitor, is compared with imatinib (Gleevec) in this phase III trial. Investigators ask whether it can improve progression-free survival; overall survival is a secondary outcome measure.

Key entry or exclusion criteria: Patients must have metastatic or locally advanced nonresectable or recurrent postsurgery GIST.

Locations: 43 sites.

Goal: 222 patients.

Study sponsor: AB Science.

Links for more information: clinicaltrials.gov/ct2/show/study/NCT00812240

NIH clinical trials identifier: NCT00812240

Objectives: Masitinib, a novel, multitargeted, tyrosine kinase inhibitor, is compared with imatinib (Gleevec) in this phase III trial. Investigators ask whether it can improve progression-free survival; overall survival is a secondary outcome measure.

Key entry or exclusion criteria: Patients must have metastatic or locally advanced nonresectable or recurrent postsurgery GIST.

Locations: 43 sites.

Goal: 222 patients.

Study sponsor: AB Science.

Links for more information: clinicaltrials.gov/ct2/show/study/NCT00812240

NIH clinical trials identifier: NCT00812240

Objectives: Trabectedin (Yondelis) is approved for sarcoma treatment in many countries outside the United States. This open-label, phase III trial asks whether it can improve overall survival compared with dacarbazine in patients with advanced L-sarcoma.

Key entry or exclusion criteria: Patients must have advanced or spreading disease. They cannot have had prior exposure to the study drugs or have received the last dose of any therapy less than 3 weeks previously.

Locations: 73 sites.

Goal: 570 patients.

Study sponsor: Johnson & Johnson Pharmaceutical Research & Development LLC in collaboration with PharmaMar.

Links for more information: clinicaltrials.gov/ct2/show/study/NCT01343277

NIH clinical trials identifier: NCT01343277

Objectives: Trabectedin (Yondelis) is approved for sarcoma treatment in many countries outside the United States. This open-label, phase III trial asks whether it can improve overall survival compared with dacarbazine in patients with advanced L-sarcoma.

Key entry or exclusion criteria: Patients must have advanced or spreading disease. They cannot have had prior exposure to the study drugs or have received the last dose of any therapy less than 3 weeks previously.

Locations: 73 sites.

Goal: 570 patients.

Study sponsor: Johnson & Johnson Pharmaceutical Research & Development LLC in collaboration with PharmaMar.

Links for more information: clinicaltrials.gov/ct2/show/study/NCT01343277

NIH clinical trials identifier: NCT01343277

Objectives: Trabectedin (Yondelis) is approved for sarcoma treatment in many countries outside the United States. This open-label, phase III trial asks whether it can improve overall survival compared with dacarbazine in patients with advanced L-sarcoma.

Key entry or exclusion criteria: Patients must have advanced or spreading disease. They cannot have had prior exposure to the study drugs or have received the last dose of any therapy less than 3 weeks previously.

Locations: 73 sites.

Goal: 570 patients.

Study sponsor: Johnson & Johnson Pharmaceutical Research & Development LLC in collaboration with PharmaMar.

Links for more information: clinicaltrials.gov/ct2/show/study/NCT01343277

NIH clinical trials identifier: NCT01343277

Objectives: A synthetic mustard, palifosfamide-tris may overcome the tumor resistance seen with ifosfamide. Investigators will compare progression-free survival followed by overall survival when this investigative agent is added to standard therapy with doxorubicin.

Key entry or exclusion criteria: Patients must have untreated metastatic disease. They may not have specific sarcoma histological subtypes including GIST and Ewing’s sarcoma, or any other prior or current systemic therapy for metastatic sarcoma.

Locations: 164 sites.

Goal: 424 patients.

Study sponsor: Ziopharm Oncology Inc.

Links for more information: clinicaltrials.gov/ct2/show/NCT01168791

NIH clinical trials identifier: NCT01168791

Objectives: A synthetic mustard, palifosfamide-tris may overcome the tumor resistance seen with ifosfamide. Investigators will compare progression-free survival followed by overall survival when this investigative agent is added to standard therapy with doxorubicin.

Key entry or exclusion criteria: Patients must have untreated metastatic disease. They may not have specific sarcoma histological subtypes including GIST and Ewing’s sarcoma, or any other prior or current systemic therapy for metastatic sarcoma.

Locations: 164 sites.

Goal: 424 patients.

Study sponsor: Ziopharm Oncology Inc.

Links for more information: clinicaltrials.gov/ct2/show/NCT01168791

NIH clinical trials identifier: NCT01168791

Objectives: A synthetic mustard, palifosfamide-tris may overcome the tumor resistance seen with ifosfamide. Investigators will compare progression-free survival followed by overall survival when this investigative agent is added to standard therapy with doxorubicin.

Key entry or exclusion criteria: Patients must have untreated metastatic disease. They may not have specific sarcoma histological subtypes including GIST and Ewing’s sarcoma, or any other prior or current systemic therapy for metastatic sarcoma.

Locations: 164 sites.

Goal: 424 patients.

Study sponsor: Ziopharm Oncology Inc.

Links for more information: clinicaltrials.gov/ct2/show/NCT01168791

NIH clinical trials identifier: NCT01168791

VIENNA – A more aggressive combination of doxorubicin and ifosfamide provided no significant overall survival advantage over single-agent doxorubicin as first-line chemotherapy in advanced soft-tissue sarcoma in a phase III trial.

The European Organisation for Research and Treatment of Cancer (EORTC) 62012 study’s primary end point of median overall survival reached 14.3 months with the combination and 12.8 months with doxorubicin alone (hazard ratio, 0.83; P = .076). One-year survival rates were 60% and 51%, respectively.

Patrice Wendling/IMNG Medical Media

As previously observed, the combination of doxorubicin (Adriamycin) and ifosfamide (Ifex) increased response rates and progression-free survival, but at a cost of considerably more toxicity. "The standard treatment remains single-agent doxorubicin," Dr. Winette van der Graaf said during a Presidential Symposium at the European Society for Medical Oncology Congress.

Combination therapy, she added, can be considered if surgery for unresectable tumors or curative metastasectomy is foreseen, and may be an option for highly symptomatic patients without comorbidity, although the pros and cons should be discussed with the patient.

"The advantage of having the results of this study is that it’s easier now to have this discussion with the patient," said Dr. van der Graaf, of Radboud University Nijmegen (Netherlands) Medical Centre.

The EORTC Soft Tissue and Bone Sarcoma Group designed the trial to answer the long-standing question of whether single-agent doxorubicin or doxorubicin plus ifosfamide is the best first-line treatment for metastatic soft-tissue sarcomas. An earlier EORTC phase III trial (J. Clin. Oncol. 1995;13:1537-45) explored the combination at a lower dose of ifosfamide than is used today, with more recent phase II trials suggesting that a higher dose could increase response rates and progression-free survival.

EORTC 62012 investigators at 38 centers in nine countries randomly assigned 455 patients, aged 18-60 years, with locally advanced unresectable or metastatic soft-tissue sarcoma to receive doxorubicin 75 mg/m² bolus on day 1 or as a 72-hour continuous IV infusion or doxorubicin 25 mg/m² on days 1-3 plus ifosfamide 2.5 g/m² on days 1-4 and pegfilgrastim 6 mg subcutaneous on day 5.

Patients were stratified by age, performance status (0 vs. 1), liver metastases, and histological grade. No prior chemotherapy was allowed for advanced disease.

After a median follow-up of 56 months, median progression-free survival increased significantly from 4.6 months with single-agent doxorubicin to 7.4 months with the addition of ifosfamide (HR 0.74, P = .003), Dr. van der Graaf reported on behalf of lead author Dr. Ian Judson of the Royal Marsden Hospital, London.

Subgroup analyses revealed significantly longer progression-free survival among patients aged 40-49 years, but this significance disappeared when all patients under age 50 were included in the analysis. No subgroups had significantly better overall survival.

The complete response rate was very low, at 0.4% in the doxorubicin arm and 1.8% in the combination arm. Remarkably, partial responses doubled with combination therapy from 13.2% to 24.7%, but overall response rates (13.6% vs. 26.5%) were far less than expected from phase II trials, where they ranged from 52% to 66%, she observed.

At first blush, the difference in progression-free survival with combination therapy may not appear that important, but from the perspective of patients with metastatic soft-tissue sarcoma, who typically have a median survival of only 1 year, this means that they’ll spend about 20% of their lifetime longer with disease control, said discussant Dr. George Demetri, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute in Boston.

Patrice Wendling/IMNG Medical Media

"The question for us as clinicians is can we target patients who truly would get more benefit from this kind of doubling of tumor response and control, despite the sizable toxicities of the more toxic combination chemotherapy," he said.

Dr. Demetri pointed out that significantly more patients discontinued combination therapy than single-agent doxorubicin due to toxicity (40 patients vs. 6 patients). The most common grade 3 or higher adverse events in the combination and doxorubicin arms were febrile neutropenia (46% vs. 13.5%), anemia (35% vs. 4.6%) and thrombocytopenia (33.5% vs. 0.4%).

Dr. Demetri cautioned that the results should not be blindly extrapolated to clinical practice because patients in the trial were younger and healthier than those typically seen in practice. However, the solid data can be used to make informed choices, he said.

If a patient is asymptomatic, as many metastatic sarcoma patients are, then single-agent doxorubicin, which he described as a strong, aggressive, "truck" of a therapy, "may be sufficient" and "more kind, more humane" to the patient, he said. If the patient is symptomatic or tumor shrinkage is required to improve quality of life because of tumor-related pain, "then perhaps combination therapy, although more toxic, may be more beneficial," he added.

The EORTC sponsored the trial. Dr. van der Graaf and Dr. Judson reported no conflicts of interest. Dr. Demetri reported financial relationships with several pharmaceutical companies.

VIENNA – A more aggressive combination of doxorubicin and ifosfamide provided no significant overall survival advantage over single-agent doxorubicin as first-line chemotherapy in advanced soft-tissue sarcoma in a phase III trial.

The European Organisation for Research and Treatment of Cancer (EORTC) 62012 study’s primary end point of median overall survival reached 14.3 months with the combination and 12.8 months with doxorubicin alone (hazard ratio, 0.83; P = .076). One-year survival rates were 60% and 51%, respectively.

Patrice Wendling/IMNG Medical Media

As previously observed, the combination of doxorubicin (Adriamycin) and ifosfamide (Ifex) increased response rates and progression-free survival, but at a cost of considerably more toxicity. "The standard treatment remains single-agent doxorubicin," Dr. Winette van der Graaf said during a Presidential Symposium at the European Society for Medical Oncology Congress.

Combination therapy, she added, can be considered if surgery for unresectable tumors or curative metastasectomy is foreseen, and may be an option for highly symptomatic patients without comorbidity, although the pros and cons should be discussed with the patient.

"The advantage of having the results of this study is that it’s easier now to have this discussion with the patient," said Dr. van der Graaf, of Radboud University Nijmegen (Netherlands) Medical Centre.

The EORTC Soft Tissue and Bone Sarcoma Group designed the trial to answer the long-standing question of whether single-agent doxorubicin or doxorubicin plus ifosfamide is the best first-line treatment for metastatic soft-tissue sarcomas. An earlier EORTC phase III trial (J. Clin. Oncol. 1995;13:1537-45) explored the combination at a lower dose of ifosfamide than is used today, with more recent phase II trials suggesting that a higher dose could increase response rates and progression-free survival.

EORTC 62012 investigators at 38 centers in nine countries randomly assigned 455 patients, aged 18-60 years, with locally advanced unresectable or metastatic soft-tissue sarcoma to receive doxorubicin 75 mg/m² bolus on day 1 or as a 72-hour continuous IV infusion or doxorubicin 25 mg/m² on days 1-3 plus ifosfamide 2.5 g/m² on days 1-4 and pegfilgrastim 6 mg subcutaneous on day 5.

Patients were stratified by age, performance status (0 vs. 1), liver metastases, and histological grade. No prior chemotherapy was allowed for advanced disease.

After a median follow-up of 56 months, median progression-free survival increased significantly from 4.6 months with single-agent doxorubicin to 7.4 months with the addition of ifosfamide (HR 0.74, P = .003), Dr. van der Graaf reported on behalf of lead author Dr. Ian Judson of the Royal Marsden Hospital, London.

Subgroup analyses revealed significantly longer progression-free survival among patients aged 40-49 years, but this significance disappeared when all patients under age 50 were included in the analysis. No subgroups had significantly better overall survival.

The complete response rate was very low, at 0.4% in the doxorubicin arm and 1.8% in the combination arm. Remarkably, partial responses doubled with combination therapy from 13.2% to 24.7%, but overall response rates (13.6% vs. 26.5%) were far less than expected from phase II trials, where they ranged from 52% to 66%, she observed.

At first blush, the difference in progression-free survival with combination therapy may not appear that important, but from the perspective of patients with metastatic soft-tissue sarcoma, who typically have a median survival of only 1 year, this means that they’ll spend about 20% of their lifetime longer with disease control, said discussant Dr. George Demetri, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute in Boston.

Patrice Wendling/IMNG Medical Media

"The question for us as clinicians is can we target patients who truly would get more benefit from this kind of doubling of tumor response and control, despite the sizable toxicities of the more toxic combination chemotherapy," he said.

Dr. Demetri pointed out that significantly more patients discontinued combination therapy than single-agent doxorubicin due to toxicity (40 patients vs. 6 patients). The most common grade 3 or higher adverse events in the combination and doxorubicin arms were febrile neutropenia (46% vs. 13.5%), anemia (35% vs. 4.6%) and thrombocytopenia (33.5% vs. 0.4%).

Dr. Demetri cautioned that the results should not be blindly extrapolated to clinical practice because patients in the trial were younger and healthier than those typically seen in practice. However, the solid data can be used to make informed choices, he said.

If a patient is asymptomatic, as many metastatic sarcoma patients are, then single-agent doxorubicin, which he described as a strong, aggressive, "truck" of a therapy, "may be sufficient" and "more kind, more humane" to the patient, he said. If the patient is symptomatic or tumor shrinkage is required to improve quality of life because of tumor-related pain, "then perhaps combination therapy, although more toxic, may be more beneficial," he added.

The EORTC sponsored the trial. Dr. van der Graaf and Dr. Judson reported no conflicts of interest. Dr. Demetri reported financial relationships with several pharmaceutical companies.

VIENNA – A more aggressive combination of doxorubicin and ifosfamide provided no significant overall survival advantage over single-agent doxorubicin as first-line chemotherapy in advanced soft-tissue sarcoma in a phase III trial.

The European Organisation for Research and Treatment of Cancer (EORTC) 62012 study’s primary end point of median overall survival reached 14.3 months with the combination and 12.8 months with doxorubicin alone (hazard ratio, 0.83; P = .076). One-year survival rates were 60% and 51%, respectively.

Patrice Wendling/IMNG Medical Media

As previously observed, the combination of doxorubicin (Adriamycin) and ifosfamide (Ifex) increased response rates and progression-free survival, but at a cost of considerably more toxicity. "The standard treatment remains single-agent doxorubicin," Dr. Winette van der Graaf said during a Presidential Symposium at the European Society for Medical Oncology Congress.

Combination therapy, she added, can be considered if surgery for unresectable tumors or curative metastasectomy is foreseen, and may be an option for highly symptomatic patients without comorbidity, although the pros and cons should be discussed with the patient.

"The advantage of having the results of this study is that it’s easier now to have this discussion with the patient," said Dr. van der Graaf, of Radboud University Nijmegen (Netherlands) Medical Centre.

The EORTC Soft Tissue and Bone Sarcoma Group designed the trial to answer the long-standing question of whether single-agent doxorubicin or doxorubicin plus ifosfamide is the best first-line treatment for metastatic soft-tissue sarcomas. An earlier EORTC phase III trial (J. Clin. Oncol. 1995;13:1537-45) explored the combination at a lower dose of ifosfamide than is used today, with more recent phase II trials suggesting that a higher dose could increase response rates and progression-free survival.

EORTC 62012 investigators at 38 centers in nine countries randomly assigned 455 patients, aged 18-60 years, with locally advanced unresectable or metastatic soft-tissue sarcoma to receive doxorubicin 75 mg/m² bolus on day 1 or as a 72-hour continuous IV infusion or doxorubicin 25 mg/m² on days 1-3 plus ifosfamide 2.5 g/m² on days 1-4 and pegfilgrastim 6 mg subcutaneous on day 5.

Patients were stratified by age, performance status (0 vs. 1), liver metastases, and histological grade. No prior chemotherapy was allowed for advanced disease.

After a median follow-up of 56 months, median progression-free survival increased significantly from 4.6 months with single-agent doxorubicin to 7.4 months with the addition of ifosfamide (HR 0.74, P = .003), Dr. van der Graaf reported on behalf of lead author Dr. Ian Judson of the Royal Marsden Hospital, London.

Subgroup analyses revealed significantly longer progression-free survival among patients aged 40-49 years, but this significance disappeared when all patients under age 50 were included in the analysis. No subgroups had significantly better overall survival.

The complete response rate was very low, at 0.4% in the doxorubicin arm and 1.8% in the combination arm. Remarkably, partial responses doubled with combination therapy from 13.2% to 24.7%, but overall response rates (13.6% vs. 26.5%) were far less than expected from phase II trials, where they ranged from 52% to 66%, she observed.

At first blush, the difference in progression-free survival with combination therapy may not appear that important, but from the perspective of patients with metastatic soft-tissue sarcoma, who typically have a median survival of only 1 year, this means that they’ll spend about 20% of their lifetime longer with disease control, said discussant Dr. George Demetri, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute in Boston.

Patrice Wendling/IMNG Medical Media

"The question for us as clinicians is can we target patients who truly would get more benefit from this kind of doubling of tumor response and control, despite the sizable toxicities of the more toxic combination chemotherapy," he said.

Dr. Demetri pointed out that significantly more patients discontinued combination therapy than single-agent doxorubicin due to toxicity (40 patients vs. 6 patients). The most common grade 3 or higher adverse events in the combination and doxorubicin arms were febrile neutropenia (46% vs. 13.5%), anemia (35% vs. 4.6%) and thrombocytopenia (33.5% vs. 0.4%).

Dr. Demetri cautioned that the results should not be blindly extrapolated to clinical practice because patients in the trial were younger and healthier than those typically seen in practice. However, the solid data can be used to make informed choices, he said.

If a patient is asymptomatic, as many metastatic sarcoma patients are, then single-agent doxorubicin, which he described as a strong, aggressive, "truck" of a therapy, "may be sufficient" and "more kind, more humane" to the patient, he said. If the patient is symptomatic or tumor shrinkage is required to improve quality of life because of tumor-related pain, "then perhaps combination therapy, although more toxic, may be more beneficial," he added.

The EORTC sponsored the trial. Dr. van der Graaf and Dr. Judson reported no conflicts of interest. Dr. Demetri reported financial relationships with several pharmaceutical companies.

Kaposi's sarcoma is making a comeback in aging HIV patients, even among those with well-controlled disease. Dr. Kieron S. Leslie, an associate clinical professor of dermatology at the University of California, San Francisco, discusses the cancer's return and its implications for patients with HIV.

Kaposi's sarcoma is making a comeback in aging HIV patients, even among those with well-controlled disease. Dr. Kieron S. Leslie, an associate clinical professor of dermatology at the University of California, San Francisco, discusses the cancer's return and its implications for patients with HIV.

Kaposi's sarcoma is making a comeback in aging HIV patients, even among those with well-controlled disease. Dr. Kieron S. Leslie, an associate clinical professor of dermatology at the University of California, San Francisco, discusses the cancer's return and its implications for patients with HIV.

Anemia drugs sold under the brand names of Procrit, Aranesp, and Epogen come under new and scathing scrutiny in an exclusive report published July 20 in the Washington Post.

The investigative article by Peter Whoriskey alleges that pharmaceutical giants Amgen and Johnson & Johnson "wildly overstated" benefits while understating potentially lethal side effects of these erythropoiesis-stimulating agents (ESAs).

While safety trials required by the Food and Drug Administration lagged for more than a decade, the companies successfully lobbied for a payment system that rewarded physicians for giving large doses of their high-priced drugs, according to the report.

Use of the drugs declined in recent years after studies showed higher mortality rates in patients given ESAs. Epoetin-alfa (Procrit and Epogen) and darbepoetin alfa (Aranesp) are used to treat anemia in patients undergoing cancer chemotherapy or dialysis for chronic kidney disease.

Anemia drugs sold under the brand names of Procrit, Aranesp, and Epogen come under new and scathing scrutiny in an exclusive report published July 20 in the Washington Post.

The investigative article by Peter Whoriskey alleges that pharmaceutical giants Amgen and Johnson & Johnson "wildly overstated" benefits while understating potentially lethal side effects of these erythropoiesis-stimulating agents (ESAs).

While safety trials required by the Food and Drug Administration lagged for more than a decade, the companies successfully lobbied for a payment system that rewarded physicians for giving large doses of their high-priced drugs, according to the report.

Use of the drugs declined in recent years after studies showed higher mortality rates in patients given ESAs. Epoetin-alfa (Procrit and Epogen) and darbepoetin alfa (Aranesp) are used to treat anemia in patients undergoing cancer chemotherapy or dialysis for chronic kidney disease.

Anemia drugs sold under the brand names of Procrit, Aranesp, and Epogen come under new and scathing scrutiny in an exclusive report published July 20 in the Washington Post.

The investigative article by Peter Whoriskey alleges that pharmaceutical giants Amgen and Johnson & Johnson "wildly overstated" benefits while understating potentially lethal side effects of these erythropoiesis-stimulating agents (ESAs).

While safety trials required by the Food and Drug Administration lagged for more than a decade, the companies successfully lobbied for a payment system that rewarded physicians for giving large doses of their high-priced drugs, according to the report.

Use of the drugs declined in recent years after studies showed higher mortality rates in patients given ESAs. Epoetin-alfa (Procrit and Epogen) and darbepoetin alfa (Aranesp) are used to treat anemia in patients undergoing cancer chemotherapy or dialysis for chronic kidney disease.

Preliminary data indicate that a single 32-mg intravenous dose of ondansetron should be avoided because it may increase the risk of QT prolongation, along with the potentially fatal arrhythmia torsades de pointes, the Food and Drug Administration has announced.

GlaxoSmithKline, which manufactures ondansetron (Zofran), is removing the 32-mg single IV dose from the antinausea and vomiting drug’s label, according to an FDA statement.

The updated label will say that ondansetron, a 5-HT₃ receptor antagonist, can continue to be used to treat adults and children with chemotherapy-induced nausea and vomiting at the dose of 0.15 mg/kg administered every 4 hours for three doses. "However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation," the FDA said.

The new data do not affect recommendations for oral doses of ondansetron (including the single 24-mg oral dose) used for chemotherapy-induced nausea and vomiting, the FDA noted. Recommendations on lower IV doses that are used to prevent postoperative nausea and vomiting (the other approved indication for ondansetron) also are unaffected.

Preliminary results of a study conducted by GlaxoSmithKline showed that QT prolongation "occurs in a dose-dependent manner," the FDA said. At the highest dose tested (the single 32-mg IV dose), the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower single dose tested (8 mg), the maximum mean difference in QTcF from placebo after baseline correction was 6 msec.

The FDA, which required GlaxoSmithKline to conduct the study, "will evaluate the final study results when available, and will work with GSK to explore an alternative single dose regimen that is both safe and effective for the prevention of chemotherapy-induced nausea and vomiting in adults," the FDA said.

It pointed out that ECG changes, including QT interval prolongation and torsades de pointes, have been reported in patients treated with ondansetron. In September 2011, the agency announced that it was reviewing the potential for QT prolongation with ondansetron.

Patients who have congenital long QT syndrome, heart failure, or bradyarrhythmias, or who are taking other medications that prolong the QT interval "may be at particular risk for QT prolongation" with ondansetron, the FDA warned.

The statement is available at www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

Preliminary data indicate that a single 32-mg intravenous dose of ondansetron should be avoided because it may increase the risk of QT prolongation, along with the potentially fatal arrhythmia torsades de pointes, the Food and Drug Administration has announced.

GlaxoSmithKline, which manufactures ondansetron (Zofran), is removing the 32-mg single IV dose from the antinausea and vomiting drug’s label, according to an FDA statement.

The updated label will say that ondansetron, a 5-HT₃ receptor antagonist, can continue to be used to treat adults and children with chemotherapy-induced nausea and vomiting at the dose of 0.15 mg/kg administered every 4 hours for three doses. "However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation," the FDA said.

The new data do not affect recommendations for oral doses of ondansetron (including the single 24-mg oral dose) used for chemotherapy-induced nausea and vomiting, the FDA noted. Recommendations on lower IV doses that are used to prevent postoperative nausea and vomiting (the other approved indication for ondansetron) also are unaffected.

Preliminary results of a study conducted by GlaxoSmithKline showed that QT prolongation "occurs in a dose-dependent manner," the FDA said. At the highest dose tested (the single 32-mg IV dose), the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower single dose tested (8 mg), the maximum mean difference in QTcF from placebo after baseline correction was 6 msec.

The FDA, which required GlaxoSmithKline to conduct the study, "will evaluate the final study results when available, and will work with GSK to explore an alternative single dose regimen that is both safe and effective for the prevention of chemotherapy-induced nausea and vomiting in adults," the FDA said.

It pointed out that ECG changes, including QT interval prolongation and torsades de pointes, have been reported in patients treated with ondansetron. In September 2011, the agency announced that it was reviewing the potential for QT prolongation with ondansetron.

Patients who have congenital long QT syndrome, heart failure, or bradyarrhythmias, or who are taking other medications that prolong the QT interval "may be at particular risk for QT prolongation" with ondansetron, the FDA warned.

The statement is available at www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

Preliminary data indicate that a single 32-mg intravenous dose of ondansetron should be avoided because it may increase the risk of QT prolongation, along with the potentially fatal arrhythmia torsades de pointes, the Food and Drug Administration has announced.

GlaxoSmithKline, which manufactures ondansetron (Zofran), is removing the 32-mg single IV dose from the antinausea and vomiting drug’s label, according to an FDA statement.

The updated label will say that ondansetron, a 5-HT₃ receptor antagonist, can continue to be used to treat adults and children with chemotherapy-induced nausea and vomiting at the dose of 0.15 mg/kg administered every 4 hours for three doses. "However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation," the FDA said.

The new data do not affect recommendations for oral doses of ondansetron (including the single 24-mg oral dose) used for chemotherapy-induced nausea and vomiting, the FDA noted. Recommendations on lower IV doses that are used to prevent postoperative nausea and vomiting (the other approved indication for ondansetron) also are unaffected.

Preliminary results of a study conducted by GlaxoSmithKline showed that QT prolongation "occurs in a dose-dependent manner," the FDA said. At the highest dose tested (the single 32-mg IV dose), the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower single dose tested (8 mg), the maximum mean difference in QTcF from placebo after baseline correction was 6 msec.

The FDA, which required GlaxoSmithKline to conduct the study, "will evaluate the final study results when available, and will work with GSK to explore an alternative single dose regimen that is both safe and effective for the prevention of chemotherapy-induced nausea and vomiting in adults," the FDA said.

It pointed out that ECG changes, including QT interval prolongation and torsades de pointes, have been reported in patients treated with ondansetron. In September 2011, the agency announced that it was reviewing the potential for QT prolongation with ondansetron.

Patients who have congenital long QT syndrome, heart failure, or bradyarrhythmias, or who are taking other medications that prolong the QT interval "may be at particular risk for QT prolongation" with ondansetron, the FDA warned.

The statement is available at www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

Three lots of leucovorin calcium injection manufactured by Bedford Laboratories have been recalled because of crystalline particulate matter that is visible in some vials, the Food and Drug Administration announced on July 6.

The nationwide recall applies to lots that were shipped between January and June 2011, and expire in 2013. The particulate matter identified is the active drug substance, according to the FDA and a statement by the company, a division of Ben Venue Laboratories in Bedford, Ohio.

Courtesy of FDA

To date, no foreign matter has been identified, both said, and no adverse reactions have been reported in association with any of the recalled lots.

Particulate matter is considered a potential health hazard in that it can case vein irritation and phlebitis, clinically occult pulmonary granulomas, local tissue infarction, severe pulmonary dysfunction, occlusion of capillaries and arteries, anaphylactic shock, and death, according to the FDA and Bedford.

Leucovorin is widely used in oncology, with indications for rescue after high-dose methotrexate administration in osteosarcoma as well as to counteract methotrexate toxicity, impaired methotrexate elimination, and inadvertent overdoses of folic acid antagonists. It is also indicated in the treatment of megaloblastic anemias caused by folic acid deficiency, when oral therapy is not feasible; and in combination with 5-fluorouracil in patients with advanced colorectal cancer.

Leucovorin is one of the generic cancer drugs in short supply, according to an FDA listing of current drug shortages. Bedford Laboratories cited "manufacturing delays" for the limited availability of its leucovorin products in an entry last updated April 10, 2012.

Lot numbers of the recalled products are: 2017620, 2038374, and 2038374A. Health care practitioners are advised to quarantine recalled vials for return to the company.

Adverse reactions associated with the recalled leucovorin lots should be reported to the manufacturer at 800-521-5169 or the FDA at 800-332-1088 or www.fda.gov/medwatch.

Three lots of leucovorin calcium injection manufactured by Bedford Laboratories have been recalled because of crystalline particulate matter that is visible in some vials, the Food and Drug Administration announced on July 6.

The nationwide recall applies to lots that were shipped between January and June 2011, and expire in 2013. The particulate matter identified is the active drug substance, according to the FDA and a statement by the company, a division of Ben Venue Laboratories in Bedford, Ohio.

Courtesy of FDA

To date, no foreign matter has been identified, both said, and no adverse reactions have been reported in association with any of the recalled lots.

Particulate matter is considered a potential health hazard in that it can case vein irritation and phlebitis, clinically occult pulmonary granulomas, local tissue infarction, severe pulmonary dysfunction, occlusion of capillaries and arteries, anaphylactic shock, and death, according to the FDA and Bedford.

Leucovorin is widely used in oncology, with indications for rescue after high-dose methotrexate administration in osteosarcoma as well as to counteract methotrexate toxicity, impaired methotrexate elimination, and inadvertent overdoses of folic acid antagonists. It is also indicated in the treatment of megaloblastic anemias caused by folic acid deficiency, when oral therapy is not feasible; and in combination with 5-fluorouracil in patients with advanced colorectal cancer.

Leucovorin is one of the generic cancer drugs in short supply, according to an FDA listing of current drug shortages. Bedford Laboratories cited "manufacturing delays" for the limited availability of its leucovorin products in an entry last updated April 10, 2012.

Lot numbers of the recalled products are: 2017620, 2038374, and 2038374A. Health care practitioners are advised to quarantine recalled vials for return to the company.

Adverse reactions associated with the recalled leucovorin lots should be reported to the manufacturer at 800-521-5169 or the FDA at 800-332-1088 or www.fda.gov/medwatch.

Three lots of leucovorin calcium injection manufactured by Bedford Laboratories have been recalled because of crystalline particulate matter that is visible in some vials, the Food and Drug Administration announced on July 6.

The nationwide recall applies to lots that were shipped between January and June 2011, and expire in 2013. The particulate matter identified is the active drug substance, according to the FDA and a statement by the company, a division of Ben Venue Laboratories in Bedford, Ohio.

Courtesy of FDA

To date, no foreign matter has been identified, both said, and no adverse reactions have been reported in association with any of the recalled lots.

Particulate matter is considered a potential health hazard in that it can case vein irritation and phlebitis, clinically occult pulmonary granulomas, local tissue infarction, severe pulmonary dysfunction, occlusion of capillaries and arteries, anaphylactic shock, and death, according to the FDA and Bedford.

Leucovorin is widely used in oncology, with indications for rescue after high-dose methotrexate administration in osteosarcoma as well as to counteract methotrexate toxicity, impaired methotrexate elimination, and inadvertent overdoses of folic acid antagonists. It is also indicated in the treatment of megaloblastic anemias caused by folic acid deficiency, when oral therapy is not feasible; and in combination with 5-fluorouracil in patients with advanced colorectal cancer.

Leucovorin is one of the generic cancer drugs in short supply, according to an FDA listing of current drug shortages. Bedford Laboratories cited "manufacturing delays" for the limited availability of its leucovorin products in an entry last updated April 10, 2012.

Lot numbers of the recalled products are: 2017620, 2038374, and 2038374A. Health care practitioners are advised to quarantine recalled vials for return to the company.

Adverse reactions associated with the recalled leucovorin lots should be reported to the manufacturer at 800-521-5169 or the FDA at 800-332-1088 or www.fda.gov/medwatch.

CHICAGO – Regorafenib, an investigational tyrosine kinase inhibitor, dramatically delayed disease progression among patients with treatment-refractory metastatic gastrointestinal stromal tumor in a phase III trial.

Median progression-free survival reached 4.8 months with regorafenib vs. 0.9 months for placebo in the GRID (GIST–Regorafenib in Disease) study (hazard ratio, 0.27; P less than .0001).

"Regorafenib has the potential to fulfill an unmet need for GIST patients progressing after imatinib and sunitinib, and potentially represents a new standard of care," said Dr. George D. Demetri, who presented the results at the annual meeting of the American Society of Clinical Oncology.

"It is immaterial whether patients in this study were on third line, fourth line, or greater line, the hazard ratios were quite similar – [showing] a significant robust effect regardless of the number of prior inhibitors that these patients had been exposed to," added Dr. Demetri, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute in Boston.

GIST, the most common sarcoma subtype, until fairly recently had no known treatment. The advent of imatinib (Gleevec) and later sunitinib (Sutent) changed the disease from one that was essentially untreatable into one that has two Food & Drug Administration–approved treatment options; with median survival increasing from 3-6 months to 5 years or more. Within just a few years of therapy, however, 90% of tumors can become resistant to the anticancer effects of both approved agents.

Regorafenib is a multitarget tyrosine kinase inhibitor (TKI), which has a high affinity for two mutated, activated kinases – KIT and platelet-derived growth factor receptor – that act as the main biological drivers of GIST, Dr. Demetri explained.

"GIST is truly addicted to KIT," he said during a press briefing. Regorafenib also targets vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR-2, RET, BRAF, and the fibroblast growth factor receptor 1.

Preclinical and early-phase clinical trials have shown regorafenib has a range of anticancer activity, including a recently published phase II trial in which it was given to patients with advanced GIST after imatinib or sunitinib failure (J. Clin. Oncol. 2012 [doi:10.1200/JCO.2011.39.9394]). These promising results, released at last year’s ASCO annual meeting, prompted the phase III, double-blind, placebo-controlled GRID trial.

GRID was a "unique academic/industrial collaboration" undertaken in 17 countries across North America, Europe, and Asia-Pacific that took just 7 months from initiation to complete patient accrual. A total of 236 patients with metastatic, unresectable GIST intolerant to or progressing despite treatment with imatinib and sunitinib were screened, with 199 randomized (2:1) to regorafenib (160 mg/day) or placebo plus best supportive care.

The median age of patients was 58 years, with 75% of regorafenib-treated patients receiving two prior lines of therapy (imatinib and sunitinib only), and 59% receiving more than two prior treatments (imatinib, sunitinib, and others). Regorafenib-treated patients also had been exposed to were nilotinib (Tasigna, 21.8%), other TKIs (1.5%), mTOR inhibitors (2.3%), and cytotoxic chemotherapy (9.8%).

Active treatment or placebo was given in 4-week cycles, with 3 weeks on, and 1 week off treatment until disease progression. After disease progression, treatment was unblinded and placebo-treated patients could cross over to active treatment and receive open-label regorafenib until the next disease progression. Patients could also continue regorafenib if the clinician felt that this was of benefit. At the next progression, however, treatment was stopped.

The primary end point was progression-free survival, which clearly favored regorafenib over placebo. Exploratory analysis suggested regorafenib is effective in all molecular subtypes of GIST, including those with exon 9 and exon 11 mutations in KIT.

Important secondary end points were disease control and overall response rates. The disease control at 12 weeks or more was 52.6% for regorafenib and 9.1% for placebo, while overall response rates were 4.5% vs. 1.5%.

Dr. Demetri noted that another important secondary end point, overall survival would be confounded if the drug worked – and indeed 85% of placebo-patients crossed over to receive regorafenib. This was an intentional part of the study design, he said.

"The hazard ratio [0.77] for overall survival trended in favor of the patients who got started on regorafenib, there was a 23% decrease in the risk of death, but that was not statistically significant," Dr. Demetri said. Median overall survival has not currently been reached for either study arm.

Grade 3 drug-related side effects included those commonly associated with multitargeting TKIs or other cancer therapies, with hypertension (22.7%), hand-foot syndrome (19.7%), diarrhea (5.3%), fatigue (2.3%), mucositis (1.5%), and alopecia (1.5%) reported, as well as a few others including nausea, constipation, and myalgia.

Discussing the trial’s findings, Grant McArthur, Ph.D., of the Peter MacCallum Cancer Center in East Melbourne, Australia, said it was a very important study.

"Regorafenib is a very interesting inhibitor that is certainly worthwhile investigating in gastrointestinal stromal tumors," he said. "Clearly, this is a positive study and there’s no doubt that regorafenib is a viable third-line treatment option now for our patients."

Dr. McArthur added, however: "Best supportive care as the comparator is one standard of care. The alternative standard of care is continuation of a KIT tyrosine kinase inhibitor," which could perhaps be further investigated.

The GRID trial was sponsored by Bayer HealthCare AG. Dr. Demetri disclosed ties with Bayer, Deciphera, GlaxoSmithKline, Infinity, Novartis, Pfizer, and Roche/Genentech. Dr. McArthur disclosed ties with Bristol-Myers-Squibb, GlaxoSmithKline, Millennium, Novartis, Pfizer, and Roche/Genentech.

CHICAGO – Regorafenib, an investigational tyrosine kinase inhibitor, dramatically delayed disease progression among patients with treatment-refractory metastatic gastrointestinal stromal tumor in a phase III trial.

Median progression-free survival reached 4.8 months with regorafenib vs. 0.9 months for placebo in the GRID (GIST–Regorafenib in Disease) study (hazard ratio, 0.27; P less than .0001).

"Regorafenib has the potential to fulfill an unmet need for GIST patients progressing after imatinib and sunitinib, and potentially represents a new standard of care," said Dr. George D. Demetri, who presented the results at the annual meeting of the American Society of Clinical Oncology.

"It is immaterial whether patients in this study were on third line, fourth line, or greater line, the hazard ratios were quite similar – [showing] a significant robust effect regardless of the number of prior inhibitors that these patients had been exposed to," added Dr. Demetri, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute in Boston.

GIST, the most common sarcoma subtype, until fairly recently had no known treatment. The advent of imatinib (Gleevec) and later sunitinib (Sutent) changed the disease from one that was essentially untreatable into one that has two Food & Drug Administration–approved treatment options; with median survival increasing from 3-6 months to 5 years or more. Within just a few years of therapy, however, 90% of tumors can become resistant to the anticancer effects of both approved agents.

Regorafenib is a multitarget tyrosine kinase inhibitor (TKI), which has a high affinity for two mutated, activated kinases – KIT and platelet-derived growth factor receptor – that act as the main biological drivers of GIST, Dr. Demetri explained.

"GIST is truly addicted to KIT," he said during a press briefing. Regorafenib also targets vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR-2, RET, BRAF, and the fibroblast growth factor receptor 1.

Preclinical and early-phase clinical trials have shown regorafenib has a range of anticancer activity, including a recently published phase II trial in which it was given to patients with advanced GIST after imatinib or sunitinib failure (J. Clin. Oncol. 2012 [doi:10.1200/JCO.2011.39.9394]). These promising results, released at last year’s ASCO annual meeting, prompted the phase III, double-blind, placebo-controlled GRID trial.

GRID was a "unique academic/industrial collaboration" undertaken in 17 countries across North America, Europe, and Asia-Pacific that took just 7 months from initiation to complete patient accrual. A total of 236 patients with metastatic, unresectable GIST intolerant to or progressing despite treatment with imatinib and sunitinib were screened, with 199 randomized (2:1) to regorafenib (160 mg/day) or placebo plus best supportive care.

The median age of patients was 58 years, with 75% of regorafenib-treated patients receiving two prior lines of therapy (imatinib and sunitinib only), and 59% receiving more than two prior treatments (imatinib, sunitinib, and others). Regorafenib-treated patients also had been exposed to were nilotinib (Tasigna, 21.8%), other TKIs (1.5%), mTOR inhibitors (2.3%), and cytotoxic chemotherapy (9.8%).

Active treatment or placebo was given in 4-week cycles, with 3 weeks on, and 1 week off treatment until disease progression. After disease progression, treatment was unblinded and placebo-treated patients could cross over to active treatment and receive open-label regorafenib until the next disease progression. Patients could also continue regorafenib if the clinician felt that this was of benefit. At the next progression, however, treatment was stopped.

The primary end point was progression-free survival, which clearly favored regorafenib over placebo. Exploratory analysis suggested regorafenib is effective in all molecular subtypes of GIST, including those with exon 9 and exon 11 mutations in KIT.

Important secondary end points were disease control and overall response rates. The disease control at 12 weeks or more was 52.6% for regorafenib and 9.1% for placebo, while overall response rates were 4.5% vs. 1.5%.

Dr. Demetri noted that another important secondary end point, overall survival would be confounded if the drug worked – and indeed 85% of placebo-patients crossed over to receive regorafenib. This was an intentional part of the study design, he said.

"The hazard ratio [0.77] for overall survival trended in favor of the patients who got started on regorafenib, there was a 23% decrease in the risk of death, but that was not statistically significant," Dr. Demetri said. Median overall survival has not currently been reached for either study arm.

Grade 3 drug-related side effects included those commonly associated with multitargeting TKIs or other cancer therapies, with hypertension (22.7%), hand-foot syndrome (19.7%), diarrhea (5.3%), fatigue (2.3%), mucositis (1.5%), and alopecia (1.5%) reported, as well as a few others including nausea, constipation, and myalgia.

Discussing the trial’s findings, Grant McArthur, Ph.D., of the Peter MacCallum Cancer Center in East Melbourne, Australia, said it was a very important study.

"Regorafenib is a very interesting inhibitor that is certainly worthwhile investigating in gastrointestinal stromal tumors," he said. "Clearly, this is a positive study and there’s no doubt that regorafenib is a viable third-line treatment option now for our patients."

Dr. McArthur added, however: "Best supportive care as the comparator is one standard of care. The alternative standard of care is continuation of a KIT tyrosine kinase inhibitor," which could perhaps be further investigated.

The GRID trial was sponsored by Bayer HealthCare AG. Dr. Demetri disclosed ties with Bayer, Deciphera, GlaxoSmithKline, Infinity, Novartis, Pfizer, and Roche/Genentech. Dr. McArthur disclosed ties with Bristol-Myers-Squibb, GlaxoSmithKline, Millennium, Novartis, Pfizer, and Roche/Genentech.

CHICAGO – Regorafenib, an investigational tyrosine kinase inhibitor, dramatically delayed disease progression among patients with treatment-refractory metastatic gastrointestinal stromal tumor in a phase III trial.

Median progression-free survival reached 4.8 months with regorafenib vs. 0.9 months for placebo in the GRID (GIST–Regorafenib in Disease) study (hazard ratio, 0.27; P less than .0001).

"Regorafenib has the potential to fulfill an unmet need for GIST patients progressing after imatinib and sunitinib, and potentially represents a new standard of care," said Dr. George D. Demetri, who presented the results at the annual meeting of the American Society of Clinical Oncology.

"It is immaterial whether patients in this study were on third line, fourth line, or greater line, the hazard ratios were quite similar – [showing] a significant robust effect regardless of the number of prior inhibitors that these patients had been exposed to," added Dr. Demetri, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute in Boston.

GIST, the most common sarcoma subtype, until fairly recently had no known treatment. The advent of imatinib (Gleevec) and later sunitinib (Sutent) changed the disease from one that was essentially untreatable into one that has two Food & Drug Administration–approved treatment options; with median survival increasing from 3-6 months to 5 years or more. Within just a few years of therapy, however, 90% of tumors can become resistant to the anticancer effects of both approved agents.

Regorafenib is a multitarget tyrosine kinase inhibitor (TKI), which has a high affinity for two mutated, activated kinases – KIT and platelet-derived growth factor receptor – that act as the main biological drivers of GIST, Dr. Demetri explained.

"GIST is truly addicted to KIT," he said during a press briefing. Regorafenib also targets vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR-2, RET, BRAF, and the fibroblast growth factor receptor 1.

Preclinical and early-phase clinical trials have shown regorafenib has a range of anticancer activity, including a recently published phase II trial in which it was given to patients with advanced GIST after imatinib or sunitinib failure (J. Clin. Oncol. 2012 [doi:10.1200/JCO.2011.39.9394]). These promising results, released at last year’s ASCO annual meeting, prompted the phase III, double-blind, placebo-controlled GRID trial.

GRID was a "unique academic/industrial collaboration" undertaken in 17 countries across North America, Europe, and Asia-Pacific that took just 7 months from initiation to complete patient accrual. A total of 236 patients with metastatic, unresectable GIST intolerant to or progressing despite treatment with imatinib and sunitinib were screened, with 199 randomized (2:1) to regorafenib (160 mg/day) or placebo plus best supportive care.

The median age of patients was 58 years, with 75% of regorafenib-treated patients receiving two prior lines of therapy (imatinib and sunitinib only), and 59% receiving more than two prior treatments (imatinib, sunitinib, and others). Regorafenib-treated patients also had been exposed to were nilotinib (Tasigna, 21.8%), other TKIs (1.5%), mTOR inhibitors (2.3%), and cytotoxic chemotherapy (9.8%).

Active treatment or placebo was given in 4-week cycles, with 3 weeks on, and 1 week off treatment until disease progression. After disease progression, treatment was unblinded and placebo-treated patients could cross over to active treatment and receive open-label regorafenib until the next disease progression. Patients could also continue regorafenib if the clinician felt that this was of benefit. At the next progression, however, treatment was stopped.

The primary end point was progression-free survival, which clearly favored regorafenib over placebo. Exploratory analysis suggested regorafenib is effective in all molecular subtypes of GIST, including those with exon 9 and exon 11 mutations in KIT.

Important secondary end points were disease control and overall response rates. The disease control at 12 weeks or more was 52.6% for regorafenib and 9.1% for placebo, while overall response rates were 4.5% vs. 1.5%.

Dr. Demetri noted that another important secondary end point, overall survival would be confounded if the drug worked – and indeed 85% of placebo-patients crossed over to receive regorafenib. This was an intentional part of the study design, he said.

"The hazard ratio [0.77] for overall survival trended in favor of the patients who got started on regorafenib, there was a 23% decrease in the risk of death, but that was not statistically significant," Dr. Demetri said. Median overall survival has not currently been reached for either study arm.

Grade 3 drug-related side effects included those commonly associated with multitargeting TKIs or other cancer therapies, with hypertension (22.7%), hand-foot syndrome (19.7%), diarrhea (5.3%), fatigue (2.3%), mucositis (1.5%), and alopecia (1.5%) reported, as well as a few others including nausea, constipation, and myalgia.

Discussing the trial’s findings, Grant McArthur, Ph.D., of the Peter MacCallum Cancer Center in East Melbourne, Australia, said it was a very important study.

"Regorafenib is a very interesting inhibitor that is certainly worthwhile investigating in gastrointestinal stromal tumors," he said. "Clearly, this is a positive study and there’s no doubt that regorafenib is a viable third-line treatment option now for our patients."

Dr. McArthur added, however: "Best supportive care as the comparator is one standard of care. The alternative standard of care is continuation of a KIT tyrosine kinase inhibitor," which could perhaps be further investigated.

The GRID trial was sponsored by Bayer HealthCare AG. Dr. Demetri disclosed ties with Bayer, Deciphera, GlaxoSmithKline, Infinity, Novartis, Pfizer, and Roche/Genentech. Dr. McArthur disclosed ties with Bristol-Myers-Squibb, GlaxoSmithKline, Millennium, Novartis, Pfizer, and Roche/Genentech.