Europe’s latest sarcoma guidelines increase emphasis on genetic profiling

MILAN – The 2014 update to the European Society of Medical Oncology’s sarcoma-management guidelines put unprecedented emphasis on genetic assessment and using the data to guide treatment.

"Molecular diagnosis is recommended as standard care" for patients with gastrointestinal stromal tumors (GIST), Dr. Jean-Yves Blay said at Sarcoma and GIST 2014, hosted by the European Society for Medical Oncology (ESMO). Identifying the genetic profile of a newly diagnosed GIST "is predictive and can guide treatment in the adjuvant setting and possibly also in the advanced phase," said Dr. Blay, professor and head of medical oncology at Claude Bernard University in Lyon, France. "Molecular characterization is increasingly an important diagnostic and prognostic tool and also helps select treatment."

The new update also strengthened the advice from past updates to centralize GIST and sarcoma management at reference centers. "What is clear from looking at past guidelines is that since 2008 we have moved toward increasingly stronger recommendations to centralize," although the panel remained unable to settle on a definition of a GIST and sarcoma reference center, Dr. Blay said.

The 2014 revision to ESMO’s guidelines for managing GIST and sarcomas is the fourth biannual revision since these guidelines first appeared in 2008. The new update will soon appear on ESMO’s website. A majority of the guidelines remain based on consensus opinion and not evidence, because the number of randomized controlled trials that have tested various aspects of management remains limited, Dr. Blay said. The lack of trials also leaves many questions unanswered, such as the best treatment for GIST that carry the D842V mutation in their PDGFRA gene or for the "wild-type" GIST that don’t have any of the described GIST mutations. "Everyone agrees we need more studies," he said.

For managing patients with advanced GIST, the new update noted that surgical removal of recurrent lesions has not been proven beneficial to patients, and that the benefit from monitoring trough levels of a tyrosine-kinase inhibitor drug also remains unproven. The new update also acknowledged a possible role for continued imatinib (Gleevec) treatment after relapse, based on results from the RIGHT (Resumption of Imatinib to Control Metastatic or Unresectable GIST After Failure of Imatinib and Sunitinib) trial (Lancet Oncol. 2013;14:1175-82). In addition, the update recognized the potential benefit of trying regorafenib (Stivarga) after patients progress on imatinib or sunitinib (Sutent) treatment, and strongly advised against treating patients with two or more tyrosine-kinase inhibitor drugs simultaneously, as this approach needs further study.

One other change to the GIST guidelines this year was a suggestion to increase the frequency of follow-up examinations during the 1-3 years following the end of adjuvant therapy, also based on consensus opinion and without firm evidence, Dr. Blay said.

The revised soft-tissue sarcoma (STS) guidelines included adoption of the bone and STS classification scheme issued by the World Health Organization last year, and endorsement of genetic analyses when the histologic diagnosis is uncertain or the tumor has an unusual presentation. The revision added stronger language promoting the need to individualize radiotherapy based on factors such as clinical presentation of the sarcoma, patient history, tumor site, and patient’s age. The revision panel could not reach a consensus on a recommended, standard adjuvant regimen.

This inability to recommend adjuvant therapies should be "no surprise because there are no data. We need to look at larger numbers of patients to identify those who would benefit from adjuvant therapy," Dr. Blay said.

For treatment of advanced STSs, the panel added pazopanib (Votrient) as a second-line treatment option, but not for patients with liposarcomas, who were not included in the trial that established pazopanib’s efficacy for metastatic STS (Lancet 2012;379:1879-86). The update also recommended identifying sarcoma subtypes genetically and matching drugs to these types using agents such as sunitinib, crizotinib (Xalkori), and cediranib (Recentin). In addition, the new update highlighted that a role for intensified follow-up of metastatic STS using computed tomography was not supported by the results of a recent randomized, controlled trial.

The 2014 guidelines also include sections for four specific STSs: retroperitoneal, uterine, desmoids, and breast. "The guidelines are expanding to organ-specific locations, something we will probably see more of" in future updates, Dr. Blay said.

Dr. Blay disclosed that he has received honoraria as a consultant to PharmaMar, and that he has received research grants from Roche, GlaxoSmithKline, and Novartis.

[email protected]

On Twitter @mitchelzoler

MILAN – The 2014 update to the European Society of Medical Oncology’s sarcoma-management guidelines put unprecedented emphasis on genetic assessment and using the data to guide treatment.

"Molecular diagnosis is recommended as standard care" for patients with gastrointestinal stromal tumors (GIST), Dr. Jean-Yves Blay said at Sarcoma and GIST 2014, hosted by the European Society for Medical Oncology (ESMO). Identifying the genetic profile of a newly diagnosed GIST "is predictive and can guide treatment in the adjuvant setting and possibly also in the advanced phase," said Dr. Blay, professor and head of medical oncology at Claude Bernard University in Lyon, France. "Molecular characterization is increasingly an important diagnostic and prognostic tool and also helps select treatment."

The new update also strengthened the advice from past updates to centralize GIST and sarcoma management at reference centers. "What is clear from looking at past guidelines is that since 2008 we have moved toward increasingly stronger recommendations to centralize," although the panel remained unable to settle on a definition of a GIST and sarcoma reference center, Dr. Blay said.

The 2014 revision to ESMO’s guidelines for managing GIST and sarcomas is the fourth biannual revision since these guidelines first appeared in 2008. The new update will soon appear on ESMO’s website. A majority of the guidelines remain based on consensus opinion and not evidence, because the number of randomized controlled trials that have tested various aspects of management remains limited, Dr. Blay said. The lack of trials also leaves many questions unanswered, such as the best treatment for GIST that carry the D842V mutation in their PDGFRA gene or for the "wild-type" GIST that don’t have any of the described GIST mutations. "Everyone agrees we need more studies," he said.

For managing patients with advanced GIST, the new update noted that surgical removal of recurrent lesions has not been proven beneficial to patients, and that the benefit from monitoring trough levels of a tyrosine-kinase inhibitor drug also remains unproven. The new update also acknowledged a possible role for continued imatinib (Gleevec) treatment after relapse, based on results from the RIGHT (Resumption of Imatinib to Control Metastatic or Unresectable GIST After Failure of Imatinib and Sunitinib) trial (Lancet Oncol. 2013;14:1175-82). In addition, the update recognized the potential benefit of trying regorafenib (Stivarga) after patients progress on imatinib or sunitinib (Sutent) treatment, and strongly advised against treating patients with two or more tyrosine-kinase inhibitor drugs simultaneously, as this approach needs further study.

One other change to the GIST guidelines this year was a suggestion to increase the frequency of follow-up examinations during the 1-3 years following the end of adjuvant therapy, also based on consensus opinion and without firm evidence, Dr. Blay said.

The revised soft-tissue sarcoma (STS) guidelines included adoption of the bone and STS classification scheme issued by the World Health Organization last year, and endorsement of genetic analyses when the histologic diagnosis is uncertain or the tumor has an unusual presentation. The revision added stronger language promoting the need to individualize radiotherapy based on factors such as clinical presentation of the sarcoma, patient history, tumor site, and patient’s age. The revision panel could not reach a consensus on a recommended, standard adjuvant regimen.

This inability to recommend adjuvant therapies should be "no surprise because there are no data. We need to look at larger numbers of patients to identify those who would benefit from adjuvant therapy," Dr. Blay said.

For treatment of advanced STSs, the panel added pazopanib (Votrient) as a second-line treatment option, but not for patients with liposarcomas, who were not included in the trial that established pazopanib’s efficacy for metastatic STS (Lancet 2012;379:1879-86). The update also recommended identifying sarcoma subtypes genetically and matching drugs to these types using agents such as sunitinib, crizotinib (Xalkori), and cediranib (Recentin). In addition, the new update highlighted that a role for intensified follow-up of metastatic STS using computed tomography was not supported by the results of a recent randomized, controlled trial.

The 2014 guidelines also include sections for four specific STSs: retroperitoneal, uterine, desmoids, and breast. "The guidelines are expanding to organ-specific locations, something we will probably see more of" in future updates, Dr. Blay said.

Dr. Blay disclosed that he has received honoraria as a consultant to PharmaMar, and that he has received research grants from Roche, GlaxoSmithKline, and Novartis.

[email protected]

On Twitter @mitchelzoler

MILAN – The 2014 update to the European Society of Medical Oncology’s sarcoma-management guidelines put unprecedented emphasis on genetic assessment and using the data to guide treatment.

"Molecular diagnosis is recommended as standard care" for patients with gastrointestinal stromal tumors (GIST), Dr. Jean-Yves Blay said at Sarcoma and GIST 2014, hosted by the European Society for Medical Oncology (ESMO). Identifying the genetic profile of a newly diagnosed GIST "is predictive and can guide treatment in the adjuvant setting and possibly also in the advanced phase," said Dr. Blay, professor and head of medical oncology at Claude Bernard University in Lyon, France. "Molecular characterization is increasingly an important diagnostic and prognostic tool and also helps select treatment."

The new update also strengthened the advice from past updates to centralize GIST and sarcoma management at reference centers. "What is clear from looking at past guidelines is that since 2008 we have moved toward increasingly stronger recommendations to centralize," although the panel remained unable to settle on a definition of a GIST and sarcoma reference center, Dr. Blay said.

The 2014 revision to ESMO’s guidelines for managing GIST and sarcomas is the fourth biannual revision since these guidelines first appeared in 2008. The new update will soon appear on ESMO’s website. A majority of the guidelines remain based on consensus opinion and not evidence, because the number of randomized controlled trials that have tested various aspects of management remains limited, Dr. Blay said. The lack of trials also leaves many questions unanswered, such as the best treatment for GIST that carry the D842V mutation in their PDGFRA gene or for the "wild-type" GIST that don’t have any of the described GIST mutations. "Everyone agrees we need more studies," he said.

For managing patients with advanced GIST, the new update noted that surgical removal of recurrent lesions has not been proven beneficial to patients, and that the benefit from monitoring trough levels of a tyrosine-kinase inhibitor drug also remains unproven. The new update also acknowledged a possible role for continued imatinib (Gleevec) treatment after relapse, based on results from the RIGHT (Resumption of Imatinib to Control Metastatic or Unresectable GIST After Failure of Imatinib and Sunitinib) trial (Lancet Oncol. 2013;14:1175-82). In addition, the update recognized the potential benefit of trying regorafenib (Stivarga) after patients progress on imatinib or sunitinib (Sutent) treatment, and strongly advised against treating patients with two or more tyrosine-kinase inhibitor drugs simultaneously, as this approach needs further study.

One other change to the GIST guidelines this year was a suggestion to increase the frequency of follow-up examinations during the 1-3 years following the end of adjuvant therapy, also based on consensus opinion and without firm evidence, Dr. Blay said.

The revised soft-tissue sarcoma (STS) guidelines included adoption of the bone and STS classification scheme issued by the World Health Organization last year, and endorsement of genetic analyses when the histologic diagnosis is uncertain or the tumor has an unusual presentation. The revision added stronger language promoting the need to individualize radiotherapy based on factors such as clinical presentation of the sarcoma, patient history, tumor site, and patient’s age. The revision panel could not reach a consensus on a recommended, standard adjuvant regimen.

This inability to recommend adjuvant therapies should be "no surprise because there are no data. We need to look at larger numbers of patients to identify those who would benefit from adjuvant therapy," Dr. Blay said.

For treatment of advanced STSs, the panel added pazopanib (Votrient) as a second-line treatment option, but not for patients with liposarcomas, who were not included in the trial that established pazopanib’s efficacy for metastatic STS (Lancet 2012;379:1879-86). The update also recommended identifying sarcoma subtypes genetically and matching drugs to these types using agents such as sunitinib, crizotinib (Xalkori), and cediranib (Recentin). In addition, the new update highlighted that a role for intensified follow-up of metastatic STS using computed tomography was not supported by the results of a recent randomized, controlled trial.

The 2014 guidelines also include sections for four specific STSs: retroperitoneal, uterine, desmoids, and breast. "The guidelines are expanding to organ-specific locations, something we will probably see more of" in future updates, Dr. Blay said.

Dr. Blay disclosed that he has received honoraria as a consultant to PharmaMar, and that he has received research grants from Roche, GlaxoSmithKline, and Novartis.

[email protected]

On Twitter @mitchelzoler