Sarcoma & GIST

After surgery for high-risk gastrointestinal stromal tumor (GIST), patients who received adjuvant imatinib for 3 years achieved longer relapse-free survival (RFS) and overall survival (OS) compared with those treated for 1 year, according to a study published online in Journal of Clinical Oncology.

With a median follow up of 7.5 years, the 5-year survival rates of greater than 90% represent the highest reported to date in high-risk GIST.

“We speculate that, other than adjuvant imatinib, two procedures were crucially important for achieving the high overall survival rates: longitudinal monitoring of the abdomen with CT to detect GIST recurrence early when the tumor bulk was still small and restarting of imatinib after recurrence was detected,” wrote Dr. Heikki Joensuu of the Comprehensive Cancer Center Helsinki and University of Helsinki, Finland, and colleagues.

Five-year RFS rates for 3- and 1-year treatment durations were 71.1% and 52.3%, respectively (hazard ratio, 0.60; 95% CI, 0.44-0.81; P less than .001); 5-year OS rates were 91.9% and 85.3%, respectively (HR, 0.60; 95% CI, 0.37-0.97; P = .036), the investigators reported (J Clin Oncol. 2015 Nov. 2. doi: 10.1200/JCO.2015.62.9170).

After a median follow up of 90 months, the second planned analysis of the open-label Scandinavian Sarcoma Group XVIII/AIO study evaluated outcomes of 358 patients, 181 in the 12-month group and 177 in the 36-month group. Earlier results from the SSGXVIII/AIO trial (after a 4.5-year follow up) showed significantly longer survival in patients who received imatinib for 3 years versus 1 year, and these results have informed treatment guidelines.

However, two other large randomized trials evaluated adjuvant imatinib for durations less than 3 years in patients with lower-risk GIST, and neither study found a survival benefit. The investigators point out that because low- or intermediate-risk GIST is cured with surgery alone in the great majority of patients, most do not benefit from adjuvant imatinib.

“Hypothetically, these results suggest that obtaining overall survival benefit may require durable administrations of imatinib and that the patients at high risk for recurrence are the optimal target population,” they wrote.

All but two patients reported at least one adverse event, but most events were mild. Previous reports have suggested cardiac toxicity of imatinib, but only one patient had cardiac failure, perhaps due to the low 400 mg adjuvant daily dosage.

Dr. Joensuu reported consulting or advisory roles with Blueprint Medicines, ARIAD Pharmaceuticals, and Orion Pharma. Several of his coauthors reported ties to industry sources.

After surgery for high-risk gastrointestinal stromal tumor (GIST), patients who received adjuvant imatinib for 3 years achieved longer relapse-free survival (RFS) and overall survival (OS) compared with those treated for 1 year, according to a study published online in Journal of Clinical Oncology.

With a median follow up of 7.5 years, the 5-year survival rates of greater than 90% represent the highest reported to date in high-risk GIST.

“We speculate that, other than adjuvant imatinib, two procedures were crucially important for achieving the high overall survival rates: longitudinal monitoring of the abdomen with CT to detect GIST recurrence early when the tumor bulk was still small and restarting of imatinib after recurrence was detected,” wrote Dr. Heikki Joensuu of the Comprehensive Cancer Center Helsinki and University of Helsinki, Finland, and colleagues.

Five-year RFS rates for 3- and 1-year treatment durations were 71.1% and 52.3%, respectively (hazard ratio, 0.60; 95% CI, 0.44-0.81; P less than .001); 5-year OS rates were 91.9% and 85.3%, respectively (HR, 0.60; 95% CI, 0.37-0.97; P = .036), the investigators reported (J Clin Oncol. 2015 Nov. 2. doi: 10.1200/JCO.2015.62.9170).

After a median follow up of 90 months, the second planned analysis of the open-label Scandinavian Sarcoma Group XVIII/AIO study evaluated outcomes of 358 patients, 181 in the 12-month group and 177 in the 36-month group. Earlier results from the SSGXVIII/AIO trial (after a 4.5-year follow up) showed significantly longer survival in patients who received imatinib for 3 years versus 1 year, and these results have informed treatment guidelines.

However, two other large randomized trials evaluated adjuvant imatinib for durations less than 3 years in patients with lower-risk GIST, and neither study found a survival benefit. The investigators point out that because low- or intermediate-risk GIST is cured with surgery alone in the great majority of patients, most do not benefit from adjuvant imatinib.

“Hypothetically, these results suggest that obtaining overall survival benefit may require durable administrations of imatinib and that the patients at high risk for recurrence are the optimal target population,” they wrote.

All but two patients reported at least one adverse event, but most events were mild. Previous reports have suggested cardiac toxicity of imatinib, but only one patient had cardiac failure, perhaps due to the low 400 mg adjuvant daily dosage.

Dr. Joensuu reported consulting or advisory roles with Blueprint Medicines, ARIAD Pharmaceuticals, and Orion Pharma. Several of his coauthors reported ties to industry sources.

After surgery for high-risk gastrointestinal stromal tumor (GIST), patients who received adjuvant imatinib for 3 years achieved longer relapse-free survival (RFS) and overall survival (OS) compared with those treated for 1 year, according to a study published online in Journal of Clinical Oncology.

With a median follow up of 7.5 years, the 5-year survival rates of greater than 90% represent the highest reported to date in high-risk GIST.

“We speculate that, other than adjuvant imatinib, two procedures were crucially important for achieving the high overall survival rates: longitudinal monitoring of the abdomen with CT to detect GIST recurrence early when the tumor bulk was still small and restarting of imatinib after recurrence was detected,” wrote Dr. Heikki Joensuu of the Comprehensive Cancer Center Helsinki and University of Helsinki, Finland, and colleagues.

Five-year RFS rates for 3- and 1-year treatment durations were 71.1% and 52.3%, respectively (hazard ratio, 0.60; 95% CI, 0.44-0.81; P less than .001); 5-year OS rates were 91.9% and 85.3%, respectively (HR, 0.60; 95% CI, 0.37-0.97; P = .036), the investigators reported (J Clin Oncol. 2015 Nov. 2. doi: 10.1200/JCO.2015.62.9170).

After a median follow up of 90 months, the second planned analysis of the open-label Scandinavian Sarcoma Group XVIII/AIO study evaluated outcomes of 358 patients, 181 in the 12-month group and 177 in the 36-month group. Earlier results from the SSGXVIII/AIO trial (after a 4.5-year follow up) showed significantly longer survival in patients who received imatinib for 3 years versus 1 year, and these results have informed treatment guidelines.

However, two other large randomized trials evaluated adjuvant imatinib for durations less than 3 years in patients with lower-risk GIST, and neither study found a survival benefit. The investigators point out that because low- or intermediate-risk GIST is cured with surgery alone in the great majority of patients, most do not benefit from adjuvant imatinib.

“Hypothetically, these results suggest that obtaining overall survival benefit may require durable administrations of imatinib and that the patients at high risk for recurrence are the optimal target population,” they wrote.

All but two patients reported at least one adverse event, but most events were mild. Previous reports have suggested cardiac toxicity of imatinib, but only one patient had cardiac failure, perhaps due to the low 400 mg adjuvant daily dosage.

Dr. Joensuu reported consulting or advisory roles with Blueprint Medicines, ARIAD Pharmaceuticals, and Orion Pharma. Several of his coauthors reported ties to industry sources.

A dose-intensive multiagent regimen including dose-compressed cycles of ifosfamide/etoposide and vincristine/doxorubicin/cyclophosphamide, irinotecan, and radiation resulted in improved outcomes for patients with low-risk stage IV rhabdomyosarcoma (RMS), but not for patients with high-risk disease, according to results from the Children’s Oncology Group study.

For all patients with stage IV rhabdomyosarcoma, the 3-year event-free and overall survival rates were 38% and 56%, respectively. Patients with stage IV RMS with one or fewer Oberlin risk factors had 3-year event-free survival and overall survival rates of 69% and 79%, respectively; patients with two or more Oberlin risk factors had rates of 20% and 14%, respectively (Jour Clin Oncol. 2015 Oct 26. doi: 10.1200/JCO.2015.63.4048).

©Nephron/Wikimedia Commons/Creative Commons SA 3.0

The study identified an expanded group of patients with low-risk metastatic RMS that included patients with embryonal RMS aged 10 years and older but with an Oberlin score of less than 2. The results in this group represent an improvement over previous study results. However, for the remainder of high-risk patients with alveolar RMS, different approaches are needed, according to Dr. Brenda Weigel of the University of Minnesota, Minneapolis, and her colleagues.

“Unfortunately, alveolar RMS has fewer genetic aberrations than embryonal RMS and no known recurrently mutated cancer consensus genes, which limits genetic targets available for therapeutic approaches,” they wrote.

The Children’s Oncology Group study ARST0431 enrolled 109 patients with metastatic RMS who had no prior chemotherapy or radiation treatment from 2006 to 2008.

The study combined three treatment strategies: dose intensification by interval compression, use of active agents identified in previous phase II window studies, and use of irinotecan as a radiation sensitizer. The 54-week treatment schedule began with two cycles of vincristine/irinotecan followed by interval-compressed vincristine/doxorubicin/cyclophosphamide and ifosfamide/etoposide (cycles began every 14 days), and finished with four cycles of standard vincristine/actinomycin/cyclophosphamide (VAC) and two more cycles of vincristine/irinotecan. The treatment plan also included radiation of primary and metastatic sites at week 19.

The most common nonhematologic adverse event of grade 3 or higher was diarrhea, reported in 20% of patients during the time period when they received irinotecan. Febrile neutropenia occurred in 63% of patients.

Dr. Weigel reported financial relationships with Genentech and Eli Lilly/ImClone System. Several of her coauthors reported having ties to industry sources.

A dose-intensive multiagent regimen including dose-compressed cycles of ifosfamide/etoposide and vincristine/doxorubicin/cyclophosphamide, irinotecan, and radiation resulted in improved outcomes for patients with low-risk stage IV rhabdomyosarcoma (RMS), but not for patients with high-risk disease, according to results from the Children’s Oncology Group study.

For all patients with stage IV rhabdomyosarcoma, the 3-year event-free and overall survival rates were 38% and 56%, respectively. Patients with stage IV RMS with one or fewer Oberlin risk factors had 3-year event-free survival and overall survival rates of 69% and 79%, respectively; patients with two or more Oberlin risk factors had rates of 20% and 14%, respectively (Jour Clin Oncol. 2015 Oct 26. doi: 10.1200/JCO.2015.63.4048).

©Nephron/Wikimedia Commons/Creative Commons SA 3.0

The study identified an expanded group of patients with low-risk metastatic RMS that included patients with embryonal RMS aged 10 years and older but with an Oberlin score of less than 2. The results in this group represent an improvement over previous study results. However, for the remainder of high-risk patients with alveolar RMS, different approaches are needed, according to Dr. Brenda Weigel of the University of Minnesota, Minneapolis, and her colleagues.

“Unfortunately, alveolar RMS has fewer genetic aberrations than embryonal RMS and no known recurrently mutated cancer consensus genes, which limits genetic targets available for therapeutic approaches,” they wrote.

The Children’s Oncology Group study ARST0431 enrolled 109 patients with metastatic RMS who had no prior chemotherapy or radiation treatment from 2006 to 2008.

The study combined three treatment strategies: dose intensification by interval compression, use of active agents identified in previous phase II window studies, and use of irinotecan as a radiation sensitizer. The 54-week treatment schedule began with two cycles of vincristine/irinotecan followed by interval-compressed vincristine/doxorubicin/cyclophosphamide and ifosfamide/etoposide (cycles began every 14 days), and finished with four cycles of standard vincristine/actinomycin/cyclophosphamide (VAC) and two more cycles of vincristine/irinotecan. The treatment plan also included radiation of primary and metastatic sites at week 19.

The most common nonhematologic adverse event of grade 3 or higher was diarrhea, reported in 20% of patients during the time period when they received irinotecan. Febrile neutropenia occurred in 63% of patients.

Dr. Weigel reported financial relationships with Genentech and Eli Lilly/ImClone System. Several of her coauthors reported having ties to industry sources.

A dose-intensive multiagent regimen including dose-compressed cycles of ifosfamide/etoposide and vincristine/doxorubicin/cyclophosphamide, irinotecan, and radiation resulted in improved outcomes for patients with low-risk stage IV rhabdomyosarcoma (RMS), but not for patients with high-risk disease, according to results from the Children’s Oncology Group study.

For all patients with stage IV rhabdomyosarcoma, the 3-year event-free and overall survival rates were 38% and 56%, respectively. Patients with stage IV RMS with one or fewer Oberlin risk factors had 3-year event-free survival and overall survival rates of 69% and 79%, respectively; patients with two or more Oberlin risk factors had rates of 20% and 14%, respectively (Jour Clin Oncol. 2015 Oct 26. doi: 10.1200/JCO.2015.63.4048).

©Nephron/Wikimedia Commons/Creative Commons SA 3.0

The study identified an expanded group of patients with low-risk metastatic RMS that included patients with embryonal RMS aged 10 years and older but with an Oberlin score of less than 2. The results in this group represent an improvement over previous study results. However, for the remainder of high-risk patients with alveolar RMS, different approaches are needed, according to Dr. Brenda Weigel of the University of Minnesota, Minneapolis, and her colleagues.

“Unfortunately, alveolar RMS has fewer genetic aberrations than embryonal RMS and no known recurrently mutated cancer consensus genes, which limits genetic targets available for therapeutic approaches,” they wrote.

The Children’s Oncology Group study ARST0431 enrolled 109 patients with metastatic RMS who had no prior chemotherapy or radiation treatment from 2006 to 2008.

The study combined three treatment strategies: dose intensification by interval compression, use of active agents identified in previous phase II window studies, and use of irinotecan as a radiation sensitizer. The 54-week treatment schedule began with two cycles of vincristine/irinotecan followed by interval-compressed vincristine/doxorubicin/cyclophosphamide and ifosfamide/etoposide (cycles began every 14 days), and finished with four cycles of standard vincristine/actinomycin/cyclophosphamide (VAC) and two more cycles of vincristine/irinotecan. The treatment plan also included radiation of primary and metastatic sites at week 19.

The most common nonhematologic adverse event of grade 3 or higher was diarrhea, reported in 20% of patients during the time period when they received irinotecan. Febrile neutropenia occurred in 63% of patients.

Dr. Weigel reported financial relationships with Genentech and Eli Lilly/ImClone System. Several of her coauthors reported having ties to industry sources.

The Food and Drug Administration has approved trabectedin for the treatment of advanced or unresectable liposarcomas and leiomyosarcomas that have been previously treated with anthracycline-based regimens.

Approval is based on improvements in progression-free survival in a trial of 518 participants with metastatic or recurrent leiomyosarcoma or liposarcoma, randomly assigned to receive either trabectedin (345 patients) or dacarbazine (173 patients). Median progression-free survival was 4.2 months for those in the trabectedin arm, compared with 1.5 months for those in the dacarbazine arm, according to an Oct. 23 statement issued by the FDA.

The most common side effects for those in the trabectedin arm were nausea, fatigue, vomiting, diarrhea, constipation, decreased appetite, dyspnea, headache, peripheral edema, neutropenia, thrombocytopenia, anemia, elevated liver enzymes, and decreases in albumin.

The drug label carries a warning of the risk of neutropenic sepsis, rhabdomyolysis, hepatotoxicity, extravasation, tissue necrosis, and cardiomyopathy. Women should be advised of potential risks to a developing fetus, and those who are breastfeeding should not take trabectedin, the FDA said.

Trabectedin, an alkylating drug, is marketed as Yondelis by Janssen Products of Raritan, N.J.

The label is available on the FDA website at drugsatfda.

[email protected]

On Twitter @NikolaidesLaura

The Food and Drug Administration has approved trabectedin for the treatment of advanced or unresectable liposarcomas and leiomyosarcomas that have been previously treated with anthracycline-based regimens.

Approval is based on improvements in progression-free survival in a trial of 518 participants with metastatic or recurrent leiomyosarcoma or liposarcoma, randomly assigned to receive either trabectedin (345 patients) or dacarbazine (173 patients). Median progression-free survival was 4.2 months for those in the trabectedin arm, compared with 1.5 months for those in the dacarbazine arm, according to an Oct. 23 statement issued by the FDA.

The most common side effects for those in the trabectedin arm were nausea, fatigue, vomiting, diarrhea, constipation, decreased appetite, dyspnea, headache, peripheral edema, neutropenia, thrombocytopenia, anemia, elevated liver enzymes, and decreases in albumin.

The drug label carries a warning of the risk of neutropenic sepsis, rhabdomyolysis, hepatotoxicity, extravasation, tissue necrosis, and cardiomyopathy. Women should be advised of potential risks to a developing fetus, and those who are breastfeeding should not take trabectedin, the FDA said.

Trabectedin, an alkylating drug, is marketed as Yondelis by Janssen Products of Raritan, N.J.

The label is available on the FDA website at drugsatfda.

[email protected]

On Twitter @NikolaidesLaura

The Food and Drug Administration has approved trabectedin for the treatment of advanced or unresectable liposarcomas and leiomyosarcomas that have been previously treated with anthracycline-based regimens.

Approval is based on improvements in progression-free survival in a trial of 518 participants with metastatic or recurrent leiomyosarcoma or liposarcoma, randomly assigned to receive either trabectedin (345 patients) or dacarbazine (173 patients). Median progression-free survival was 4.2 months for those in the trabectedin arm, compared with 1.5 months for those in the dacarbazine arm, according to an Oct. 23 statement issued by the FDA.

The most common side effects for those in the trabectedin arm were nausea, fatigue, vomiting, diarrhea, constipation, decreased appetite, dyspnea, headache, peripheral edema, neutropenia, thrombocytopenia, anemia, elevated liver enzymes, and decreases in albumin.

The drug label carries a warning of the risk of neutropenic sepsis, rhabdomyolysis, hepatotoxicity, extravasation, tissue necrosis, and cardiomyopathy. Women should be advised of potential risks to a developing fetus, and those who are breastfeeding should not take trabectedin, the FDA said.

Trabectedin, an alkylating drug, is marketed as Yondelis by Janssen Products of Raritan, N.J.

The label is available on the FDA website at drugsatfda.

[email protected]

On Twitter @NikolaidesLaura

Trabectedin proved superior to standard dacarbazine therapy by numerous measures but not by overall survival in an industry-sponsored phase III clinical trial reported online Sept. 14 in Journal of Clinical Oncology.

Trabectedin, which has been used extensively in Europe for a decade but has not been approved in the U.S., has a complex mechanism of action that affects several critical cell biology processes within and surrounding tumor cells. It exhibited activity against metastatic soft tissue sarcomas in several phase II trials, said Dr. George D. Demetri of the Ludwig Center at Harvard Medical School and the Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, both in Boston, and his associates.

In this study, trabectedin was assessed in 518 patients aged 15 years and older who had heavily pretreated and rapidly progressing advanced or metastatic liposarcoma or leiomyosarcoma and were treated at 85 sites in four countries. These participants were randomly assigned to receive either trabectedin (345 patients) or dacarbazine (173 patients) via central intravenous infusion in 3-week cycles.

Compared with dacarbazine, trabectedin reduced the risk of disease progression by 45% (hazard ratio, 0.55), and superior disease control was discernible at the first patient assessment at 6 weeks. Median progression-free survival was significantly longer with trabectedin (4.2 months) than with dacarbazine (1.5 months), a benefit that was consistent across all 19 subgroups of patients assessed in sensitivity analyses, regardless of disease histology, previous therapies, or any clinical characteristics. Trabectedin also bested dacarbazine with regard to objective response rate (9.9% vs. 6.9%), median duration of response (6.5 months vs. 4.2 months), achievement of stable disease (51% vs. 35%), and achievement of durable stable disease (34% vs. 19%).

Trabectedin showed only a nonsignificant 13% reduction in overall survival, which was the primary endpoint of this study. However, several previous studies have demonstrated that it can be extremely difficult to prolong overall survival despite robust improvements in progression-free survival in patients with advanced sarcomas. Given this “historical difficulty in demonstrating overall survival improvement,” the documentation of disease control such as that achieved in this study may be considered a measure of clinically relevant efficacy in this setting, Dr. Demetri and his associates wrote (J. Clin. Oncol. 2015 Sep 14 [doi:10.1200/JCO.2015.62.4734]).

Adverse events in this study population “were consistent with the well-characterized safety and toxicity profiles of both study drugs.” Toxicity was more common with trabectedin, and deaths considered to be treatment-related occurred only in the trabectedin group: three cases of sepsis/septic shock and one each of rhabdomyolysis/sepsis, renal failure, cardiac arrest, and multiorgan failure, for a treatment-related mortality of 2.1%.

Trabectedin proved superior to standard dacarbazine therapy by numerous measures but not by overall survival in an industry-sponsored phase III clinical trial reported online Sept. 14 in Journal of Clinical Oncology.

Trabectedin, which has been used extensively in Europe for a decade but has not been approved in the U.S., has a complex mechanism of action that affects several critical cell biology processes within and surrounding tumor cells. It exhibited activity against metastatic soft tissue sarcomas in several phase II trials, said Dr. George D. Demetri of the Ludwig Center at Harvard Medical School and the Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, both in Boston, and his associates.

In this study, trabectedin was assessed in 518 patients aged 15 years and older who had heavily pretreated and rapidly progressing advanced or metastatic liposarcoma or leiomyosarcoma and were treated at 85 sites in four countries. These participants were randomly assigned to receive either trabectedin (345 patients) or dacarbazine (173 patients) via central intravenous infusion in 3-week cycles.

Compared with dacarbazine, trabectedin reduced the risk of disease progression by 45% (hazard ratio, 0.55), and superior disease control was discernible at the first patient assessment at 6 weeks. Median progression-free survival was significantly longer with trabectedin (4.2 months) than with dacarbazine (1.5 months), a benefit that was consistent across all 19 subgroups of patients assessed in sensitivity analyses, regardless of disease histology, previous therapies, or any clinical characteristics. Trabectedin also bested dacarbazine with regard to objective response rate (9.9% vs. 6.9%), median duration of response (6.5 months vs. 4.2 months), achievement of stable disease (51% vs. 35%), and achievement of durable stable disease (34% vs. 19%).

Trabectedin showed only a nonsignificant 13% reduction in overall survival, which was the primary endpoint of this study. However, several previous studies have demonstrated that it can be extremely difficult to prolong overall survival despite robust improvements in progression-free survival in patients with advanced sarcomas. Given this “historical difficulty in demonstrating overall survival improvement,” the documentation of disease control such as that achieved in this study may be considered a measure of clinically relevant efficacy in this setting, Dr. Demetri and his associates wrote (J. Clin. Oncol. 2015 Sep 14 [doi:10.1200/JCO.2015.62.4734]).

Adverse events in this study population “were consistent with the well-characterized safety and toxicity profiles of both study drugs.” Toxicity was more common with trabectedin, and deaths considered to be treatment-related occurred only in the trabectedin group: three cases of sepsis/septic shock and one each of rhabdomyolysis/sepsis, renal failure, cardiac arrest, and multiorgan failure, for a treatment-related mortality of 2.1%.

Trabectedin proved superior to standard dacarbazine therapy by numerous measures but not by overall survival in an industry-sponsored phase III clinical trial reported online Sept. 14 in Journal of Clinical Oncology.

Trabectedin, which has been used extensively in Europe for a decade but has not been approved in the U.S., has a complex mechanism of action that affects several critical cell biology processes within and surrounding tumor cells. It exhibited activity against metastatic soft tissue sarcomas in several phase II trials, said Dr. George D. Demetri of the Ludwig Center at Harvard Medical School and the Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, both in Boston, and his associates.

In this study, trabectedin was assessed in 518 patients aged 15 years and older who had heavily pretreated and rapidly progressing advanced or metastatic liposarcoma or leiomyosarcoma and were treated at 85 sites in four countries. These participants were randomly assigned to receive either trabectedin (345 patients) or dacarbazine (173 patients) via central intravenous infusion in 3-week cycles.

Compared with dacarbazine, trabectedin reduced the risk of disease progression by 45% (hazard ratio, 0.55), and superior disease control was discernible at the first patient assessment at 6 weeks. Median progression-free survival was significantly longer with trabectedin (4.2 months) than with dacarbazine (1.5 months), a benefit that was consistent across all 19 subgroups of patients assessed in sensitivity analyses, regardless of disease histology, previous therapies, or any clinical characteristics. Trabectedin also bested dacarbazine with regard to objective response rate (9.9% vs. 6.9%), median duration of response (6.5 months vs. 4.2 months), achievement of stable disease (51% vs. 35%), and achievement of durable stable disease (34% vs. 19%).

Trabectedin showed only a nonsignificant 13% reduction in overall survival, which was the primary endpoint of this study. However, several previous studies have demonstrated that it can be extremely difficult to prolong overall survival despite robust improvements in progression-free survival in patients with advanced sarcomas. Given this “historical difficulty in demonstrating overall survival improvement,” the documentation of disease control such as that achieved in this study may be considered a measure of clinically relevant efficacy in this setting, Dr. Demetri and his associates wrote (J. Clin. Oncol. 2015 Sep 14 [doi:10.1200/JCO.2015.62.4734]).

Adverse events in this study population “were consistent with the well-characterized safety and toxicity profiles of both study drugs.” Toxicity was more common with trabectedin, and deaths considered to be treatment-related occurred only in the trabectedin group: three cases of sepsis/septic shock and one each of rhabdomyolysis/sepsis, renal failure, cardiac arrest, and multiorgan failure, for a treatment-related mortality of 2.1%.

Preoperative chemotherapy is feasible for high-risk localized soft-tissue sarcomas of the limbs or superficial trunk, even with concurrent radiotherapy and even in selected elderly patients, investigators reported online Sept. 7 in Journal of Clinical Oncology.

Full-dose preoperative chemotherapy now can be offered and an excellent chemotherapeutic dose intensity now can be achieved with concomitant radiotherapy in cases “when surgical reasons suggest that major preoperative shrinkage may help,” said Dr. Elena Palassini of Istituto Nazionale dei Tumori, Bologna (Italy), and her associates in the Italian Sarcoma Group and Spanish Sarcoma Group.

©BluePlanetEarth/thinkstockphotos.com

The investigators already reported the efficacy results of their international phase III randomized clinical trial assessing preoperative chemotherapy (with or without radiotherapy, at the treating physician’s discretion). In the current analysis, they focused on the toxicity data for 303 of the trial participants, all of whom had high-grade, deep, large, adult-type soft-tissue sarcomas arising from the extremities or trunk wall.

The median patient age was 48 years (range, 15-79 years), and 13% of the study population was aged 65 years or older. A total of 152 received preoperative radiotherapy along with epirubicin plus ifosfamide.

“The most interesting clinical finding was the tolerability of the combination of preoperative chemotherapy and radiotherapy,” which is particularly remarkable because patients chosen for combination treatment had the largest tumors and the most challenging presentations, the investigators wrote.

Participants who received combination preoperative therapy showed “only limited worsening of toxicities” compared with those who had preoperative chemotherapy alone, Dr. Palassini and her associates said (J Clin Oncol. 2015 Sept. 7. doi: 10.1200/JCO.2015.62.9394).

Grade 3 or 4 thrombocytopenia was more frequent with combined therapy than with chemotherapy alone, but grade 4 leukopenia and grade 3 or 4 anemia were not. There were no cases of fatal toxicity, and the rate of wound complications was not significantly higher when radiotherapy was added to chemotherapy (17.1%) than when it was not (9.9%).

Even though some patients failed to complete all planned cycles of chemotherapy or experienced dose reductions or interruptions because of toxic effects, the overall median chemotherapeutic dose index remained “excellent” at greater than 90%. This was true even in patients aged 65 years and older, which “clearly suggests the possibility of selecting and treating at least a proportion of [older] patients in the adjuvant setting with full-dose regimens.” This finding is especially important because older patients comprise 30% of those newly diagnosed as having soft-tissue sarcoma, the investigators noted.

The authors did not identify a sponsor of this study. Dr. Palassini reported having no relevant financial disclosures, and her associates reported ties to numerous industry sources.

Preoperative chemotherapy is feasible for high-risk localized soft-tissue sarcomas of the limbs or superficial trunk, even with concurrent radiotherapy and even in selected elderly patients, investigators reported online Sept. 7 in Journal of Clinical Oncology.

Full-dose preoperative chemotherapy now can be offered and an excellent chemotherapeutic dose intensity now can be achieved with concomitant radiotherapy in cases “when surgical reasons suggest that major preoperative shrinkage may help,” said Dr. Elena Palassini of Istituto Nazionale dei Tumori, Bologna (Italy), and her associates in the Italian Sarcoma Group and Spanish Sarcoma Group.

©BluePlanetEarth/thinkstockphotos.com

The investigators already reported the efficacy results of their international phase III randomized clinical trial assessing preoperative chemotherapy (with or without radiotherapy, at the treating physician’s discretion). In the current analysis, they focused on the toxicity data for 303 of the trial participants, all of whom had high-grade, deep, large, adult-type soft-tissue sarcomas arising from the extremities or trunk wall.

The median patient age was 48 years (range, 15-79 years), and 13% of the study population was aged 65 years or older. A total of 152 received preoperative radiotherapy along with epirubicin plus ifosfamide.

“The most interesting clinical finding was the tolerability of the combination of preoperative chemotherapy and radiotherapy,” which is particularly remarkable because patients chosen for combination treatment had the largest tumors and the most challenging presentations, the investigators wrote.

Participants who received combination preoperative therapy showed “only limited worsening of toxicities” compared with those who had preoperative chemotherapy alone, Dr. Palassini and her associates said (J Clin Oncol. 2015 Sept. 7. doi: 10.1200/JCO.2015.62.9394).

Grade 3 or 4 thrombocytopenia was more frequent with combined therapy than with chemotherapy alone, but grade 4 leukopenia and grade 3 or 4 anemia were not. There were no cases of fatal toxicity, and the rate of wound complications was not significantly higher when radiotherapy was added to chemotherapy (17.1%) than when it was not (9.9%).

Even though some patients failed to complete all planned cycles of chemotherapy or experienced dose reductions or interruptions because of toxic effects, the overall median chemotherapeutic dose index remained “excellent” at greater than 90%. This was true even in patients aged 65 years and older, which “clearly suggests the possibility of selecting and treating at least a proportion of [older] patients in the adjuvant setting with full-dose regimens.” This finding is especially important because older patients comprise 30% of those newly diagnosed as having soft-tissue sarcoma, the investigators noted.

The authors did not identify a sponsor of this study. Dr. Palassini reported having no relevant financial disclosures, and her associates reported ties to numerous industry sources.

Preoperative chemotherapy is feasible for high-risk localized soft-tissue sarcomas of the limbs or superficial trunk, even with concurrent radiotherapy and even in selected elderly patients, investigators reported online Sept. 7 in Journal of Clinical Oncology.

Full-dose preoperative chemotherapy now can be offered and an excellent chemotherapeutic dose intensity now can be achieved with concomitant radiotherapy in cases “when surgical reasons suggest that major preoperative shrinkage may help,” said Dr. Elena Palassini of Istituto Nazionale dei Tumori, Bologna (Italy), and her associates in the Italian Sarcoma Group and Spanish Sarcoma Group.

©BluePlanetEarth/thinkstockphotos.com

The investigators already reported the efficacy results of their international phase III randomized clinical trial assessing preoperative chemotherapy (with or without radiotherapy, at the treating physician’s discretion). In the current analysis, they focused on the toxicity data for 303 of the trial participants, all of whom had high-grade, deep, large, adult-type soft-tissue sarcomas arising from the extremities or trunk wall.

The median patient age was 48 years (range, 15-79 years), and 13% of the study population was aged 65 years or older. A total of 152 received preoperative radiotherapy along with epirubicin plus ifosfamide.

“The most interesting clinical finding was the tolerability of the combination of preoperative chemotherapy and radiotherapy,” which is particularly remarkable because patients chosen for combination treatment had the largest tumors and the most challenging presentations, the investigators wrote.

Participants who received combination preoperative therapy showed “only limited worsening of toxicities” compared with those who had preoperative chemotherapy alone, Dr. Palassini and her associates said (J Clin Oncol. 2015 Sept. 7. doi: 10.1200/JCO.2015.62.9394).

Grade 3 or 4 thrombocytopenia was more frequent with combined therapy than with chemotherapy alone, but grade 4 leukopenia and grade 3 or 4 anemia were not. There were no cases of fatal toxicity, and the rate of wound complications was not significantly higher when radiotherapy was added to chemotherapy (17.1%) than when it was not (9.9%).

Even though some patients failed to complete all planned cycles of chemotherapy or experienced dose reductions or interruptions because of toxic effects, the overall median chemotherapeutic dose index remained “excellent” at greater than 90%. This was true even in patients aged 65 years and older, which “clearly suggests the possibility of selecting and treating at least a proportion of [older] patients in the adjuvant setting with full-dose regimens.” This finding is especially important because older patients comprise 30% of those newly diagnosed as having soft-tissue sarcoma, the investigators noted.

The authors did not identify a sponsor of this study. Dr. Palassini reported having no relevant financial disclosures, and her associates reported ties to numerous industry sources.

CHICAGO – For the first time ever, a new drug has shown a survival advantage – albeit a small one – in metastatic soft tissue sarcomas, diseases that are almost without exception unresponsive to medical therapies and rapidly fatal.

In a randomized, phase III trial, median overall survival for patients with metastatic leiomyosarcoma or liposarcoma treated with eribulin (Halaven) was 13.5 months compared with 11.5 months for patients treated with dacarbazine.

“For me as a clinical oncologist, this a clinically meaningful result given the unmet need in this rare, hard-to-treat family of diseases,” said lead investigator Dr. Patrick Schöffski, professor of medicine and head of experimental oncology lab at University Hospitals in Leuven, Belgium, at the annual meeting of the American Society of Clinical Oncology.

“I’ve been an oncologist for over 20 years, and there has never been a positive sarcoma study for survival – ever,” said ASCO expert Dr. Gary K. Schwartz, chief of hematology and oncology at Columbia University, New York, who was not involved in the study. “This is the first positive sarcoma study showing a survival benefit with any chemotherapy in the history of medical oncology.”

The findings represent “a small step for cancer, and a giant step for sarcoma.” Dr. Schwartz said at a press briefing.

In an interview, he added that he was “shocked” when he found out that the survival benefit with eribulin was seen in patients with liposarcoma as well as leiomyosarcoma. “I thought that the benefit would only be in patients with leiomyosarcoma,” he said.

Leiomyosarcoma and liposarcoma, also called adipocytic sarcoma, are two of the most common histologic subtypes of highly uncommon soft tissue sarcomas. Patients with advanced metastatic sarcomas generally have a very poor prognosis and precious few treatment options.

Eribulin is a synthetic analogue of halichondrin B, a macrolide antibiotic isolated from a sea sponge that has strong cytotoxic properties. In preclinical studies, it was shown to kill cancer cells via anti-mitotic effects. It is approved in the United States for treatment of patients with metastatic breast cancer for whom at least two other lines of therapy have failed.

Dr. Schöffski and colleagues in centers in the United States, Europe, and Korea randomly assigned patients with metastatic intermediate or high-grade leiomyosarcoma or liposarcoma to receive either eribulin 1.4 mg/m² on days 1 and 8 of 21-day cycles (228 patients), or conventional therapy with dacarbazine 850, 1,000, or 1,200 mg/m² on day 1 of every 21 day cycle (224 patients).

The majority of patients had undergone at least two prior regimens for advanced disease.

The trial met its primary endpoint of an overall survival advantage, with median OS of 13.5 months for patients on eribulin, compared with 11.5 months for those on dacarbazine. The hazard ratio (HR) was 0.768 favoring eirbulin (P = .0169).

The median progression-free survival was 2.6 months in each group.

In all, 26% of patients on eribulin and 14% on dacarbazine required dose reductions, and 8% and 5%, respectively, discontinued therapy because of treatment-emergent adverse events.

The most common grade 3 or greater toxicities in each arm were neutropenia, fatigue, and nausea. The adverse events in general were in line with known safety profiles for each agent, Dr. Schöffski said.

There were 10 deaths among patients on eribulin, two of which were attributed to the drug (1 neutropenic sepsis and one sepsis). There were three deaths among patients on dacarbazine, none attributed to therapy.

In an interview, Dr. Schöffski noted that he has treated one patient, a man with dedifferentiated liposarcoma, with 46 cycles of eribulin, “so we see activity in a tumor type that is notoriously resistant to established drugs.”

He said that moving forward, investigators may wish to test eribulin in combination with other drugs, such as therapies targeted to genetic mutations, immunotherapies, or other approaches.

The study was sponsored by Eisai, Inc. Dr. Schöffski and Dr. Schwartz reported having no relevant conflicts of interest.

CHICAGO – For the first time ever, a new drug has shown a survival advantage – albeit a small one – in metastatic soft tissue sarcomas, diseases that are almost without exception unresponsive to medical therapies and rapidly fatal.

In a randomized, phase III trial, median overall survival for patients with metastatic leiomyosarcoma or liposarcoma treated with eribulin (Halaven) was 13.5 months compared with 11.5 months for patients treated with dacarbazine.

“For me as a clinical oncologist, this a clinically meaningful result given the unmet need in this rare, hard-to-treat family of diseases,” said lead investigator Dr. Patrick Schöffski, professor of medicine and head of experimental oncology lab at University Hospitals in Leuven, Belgium, at the annual meeting of the American Society of Clinical Oncology.

“I’ve been an oncologist for over 20 years, and there has never been a positive sarcoma study for survival – ever,” said ASCO expert Dr. Gary K. Schwartz, chief of hematology and oncology at Columbia University, New York, who was not involved in the study. “This is the first positive sarcoma study showing a survival benefit with any chemotherapy in the history of medical oncology.”

The findings represent “a small step for cancer, and a giant step for sarcoma.” Dr. Schwartz said at a press briefing.

In an interview, he added that he was “shocked” when he found out that the survival benefit with eribulin was seen in patients with liposarcoma as well as leiomyosarcoma. “I thought that the benefit would only be in patients with leiomyosarcoma,” he said.

Leiomyosarcoma and liposarcoma, also called adipocytic sarcoma, are two of the most common histologic subtypes of highly uncommon soft tissue sarcomas. Patients with advanced metastatic sarcomas generally have a very poor prognosis and precious few treatment options.

Eribulin is a synthetic analogue of halichondrin B, a macrolide antibiotic isolated from a sea sponge that has strong cytotoxic properties. In preclinical studies, it was shown to kill cancer cells via anti-mitotic effects. It is approved in the United States for treatment of patients with metastatic breast cancer for whom at least two other lines of therapy have failed.

Dr. Schöffski and colleagues in centers in the United States, Europe, and Korea randomly assigned patients with metastatic intermediate or high-grade leiomyosarcoma or liposarcoma to receive either eribulin 1.4 mg/m² on days 1 and 8 of 21-day cycles (228 patients), or conventional therapy with dacarbazine 850, 1,000, or 1,200 mg/m² on day 1 of every 21 day cycle (224 patients).

The majority of patients had undergone at least two prior regimens for advanced disease.

The trial met its primary endpoint of an overall survival advantage, with median OS of 13.5 months for patients on eribulin, compared with 11.5 months for those on dacarbazine. The hazard ratio (HR) was 0.768 favoring eirbulin (P = .0169).

The median progression-free survival was 2.6 months in each group.

In all, 26% of patients on eribulin and 14% on dacarbazine required dose reductions, and 8% and 5%, respectively, discontinued therapy because of treatment-emergent adverse events.

The most common grade 3 or greater toxicities in each arm were neutropenia, fatigue, and nausea. The adverse events in general were in line with known safety profiles for each agent, Dr. Schöffski said.

There were 10 deaths among patients on eribulin, two of which were attributed to the drug (1 neutropenic sepsis and one sepsis). There were three deaths among patients on dacarbazine, none attributed to therapy.

In an interview, Dr. Schöffski noted that he has treated one patient, a man with dedifferentiated liposarcoma, with 46 cycles of eribulin, “so we see activity in a tumor type that is notoriously resistant to established drugs.”

He said that moving forward, investigators may wish to test eribulin in combination with other drugs, such as therapies targeted to genetic mutations, immunotherapies, or other approaches.

The study was sponsored by Eisai, Inc. Dr. Schöffski and Dr. Schwartz reported having no relevant conflicts of interest.

CHICAGO – For the first time ever, a new drug has shown a survival advantage – albeit a small one – in metastatic soft tissue sarcomas, diseases that are almost without exception unresponsive to medical therapies and rapidly fatal.

In a randomized, phase III trial, median overall survival for patients with metastatic leiomyosarcoma or liposarcoma treated with eribulin (Halaven) was 13.5 months compared with 11.5 months for patients treated with dacarbazine.

“For me as a clinical oncologist, this a clinically meaningful result given the unmet need in this rare, hard-to-treat family of diseases,” said lead investigator Dr. Patrick Schöffski, professor of medicine and head of experimental oncology lab at University Hospitals in Leuven, Belgium, at the annual meeting of the American Society of Clinical Oncology.

“I’ve been an oncologist for over 20 years, and there has never been a positive sarcoma study for survival – ever,” said ASCO expert Dr. Gary K. Schwartz, chief of hematology and oncology at Columbia University, New York, who was not involved in the study. “This is the first positive sarcoma study showing a survival benefit with any chemotherapy in the history of medical oncology.”

The findings represent “a small step for cancer, and a giant step for sarcoma.” Dr. Schwartz said at a press briefing.

In an interview, he added that he was “shocked” when he found out that the survival benefit with eribulin was seen in patients with liposarcoma as well as leiomyosarcoma. “I thought that the benefit would only be in patients with leiomyosarcoma,” he said.

Leiomyosarcoma and liposarcoma, also called adipocytic sarcoma, are two of the most common histologic subtypes of highly uncommon soft tissue sarcomas. Patients with advanced metastatic sarcomas generally have a very poor prognosis and precious few treatment options.

Eribulin is a synthetic analogue of halichondrin B, a macrolide antibiotic isolated from a sea sponge that has strong cytotoxic properties. In preclinical studies, it was shown to kill cancer cells via anti-mitotic effects. It is approved in the United States for treatment of patients with metastatic breast cancer for whom at least two other lines of therapy have failed.

Dr. Schöffski and colleagues in centers in the United States, Europe, and Korea randomly assigned patients with metastatic intermediate or high-grade leiomyosarcoma or liposarcoma to receive either eribulin 1.4 mg/m² on days 1 and 8 of 21-day cycles (228 patients), or conventional therapy with dacarbazine 850, 1,000, or 1,200 mg/m² on day 1 of every 21 day cycle (224 patients).

The majority of patients had undergone at least two prior regimens for advanced disease.

The trial met its primary endpoint of an overall survival advantage, with median OS of 13.5 months for patients on eribulin, compared with 11.5 months for those on dacarbazine. The hazard ratio (HR) was 0.768 favoring eirbulin (P = .0169).

The median progression-free survival was 2.6 months in each group.

In all, 26% of patients on eribulin and 14% on dacarbazine required dose reductions, and 8% and 5%, respectively, discontinued therapy because of treatment-emergent adverse events.

The most common grade 3 or greater toxicities in each arm were neutropenia, fatigue, and nausea. The adverse events in general were in line with known safety profiles for each agent, Dr. Schöffski said.

There were 10 deaths among patients on eribulin, two of which were attributed to the drug (1 neutropenic sepsis and one sepsis). There were three deaths among patients on dacarbazine, none attributed to therapy.

In an interview, Dr. Schöffski noted that he has treated one patient, a man with dedifferentiated liposarcoma, with 46 cycles of eribulin, “so we see activity in a tumor type that is notoriously resistant to established drugs.”

He said that moving forward, investigators may wish to test eribulin in combination with other drugs, such as therapies targeted to genetic mutations, immunotherapies, or other approaches.

The study was sponsored by Eisai, Inc. Dr. Schöffski and Dr. Schwartz reported having no relevant conflicts of interest.

Sleep disturbances are common among patients with cancer for many reasons. Sleep problems can be present at any stage during treatment for cancer and in some patients, sleep disturbance may be the presenting symptoms that lead to the diagnosis of some types of cancer. Poor sleep impairs quality of life In people with cancer, but most do not specifically complain of sleep problems unless they are explicitly asked. Insomnia and fatigue are most common sleep disorders in this cohort, although primary sleep disorders, including obstructive sleep apnea and restless legs syndrome, which are common in the general population, have not been carefully studied in the oncology setting despite significant their impairment of quality of life.

Click on the PDF icon at the top of this introduction to read the full article.

Sleep disturbances are common among patients with cancer for many reasons. Sleep problems can be present at any stage during treatment for cancer and in some patients, sleep disturbance may be the presenting symptoms that lead to the diagnosis of some types of cancer. Poor sleep impairs quality of life In people with cancer, but most do not specifically complain of sleep problems unless they are explicitly asked. Insomnia and fatigue are most common sleep disorders in this cohort, although primary sleep disorders, including obstructive sleep apnea and restless legs syndrome, which are common in the general population, have not been carefully studied in the oncology setting despite significant their impairment of quality of life.

Click on the PDF icon at the top of this introduction to read the full article.

Sleep disturbances are common among patients with cancer for many reasons. Sleep problems can be present at any stage during treatment for cancer and in some patients, sleep disturbance may be the presenting symptoms that lead to the diagnosis of some types of cancer. Poor sleep impairs quality of life In people with cancer, but most do not specifically complain of sleep problems unless they are explicitly asked. Insomnia and fatigue are most common sleep disorders in this cohort, although primary sleep disorders, including obstructive sleep apnea and restless legs syndrome, which are common in the general population, have not been carefully studied in the oncology setting despite significant their impairment of quality of life.

Click on the PDF icon at the top of this introduction to read the full article.