Customize
Quick Links
Specialties

Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. These activites are not approved for AMA PRA Category 1 Credit

Acknowledgment of Commercial Support

This activity is supported by an educational grant from Lilly.

For further information concerning Lilly grant funding, visit www.lillygrantoffice.com.

Moving Forward From the Status Quo for the Treatment of Soft Tissue Sarcoma: Key Questions and New Answers to Optimize Outcomes PER Pulse™ Recap

PER Pulse Recap

PER Pulse™ Recap


1 of 3
PER Pulse™ Recap

The live continuing medical education activity, Moving Forward From the Status Quo for the Treatment of Soft Tissue Sarcoma: Key Questions and New Answers to Optimize Outcomes, held adjunct to an annual oncology meeting in Chicago, Illinois, featured the following experts discussing the latest clinical research on soft tissue sarcomas: George D. Demetri, MD; Robin L. Jones, BSc, MB, MRCP, MD (Res); William D. Tap, MD; and Sandra P. D’Angelo, MD. This program featured exciting lectures on cutting-edge research affecting the management of patients with these diseases. This first of 3 PER Pulse™ Recaps reviews the key drivers for choosing first-line therapy for these diseases.

Below are some highlights from Dr Tap’s lecture:

  • Conventional first-line therapy for advanced or metastatic soft tissue sarcoma is chemotherapy.
    • The phase III GeDDiS trial failed to show any significant improvements in either progression-free survival (PFS; hazard ratio [HR], 1.28; P = .07) or overall survival (OS; HR, 1.07; P = .67) with gemcitabine + docetaxel when compared with single-agent doxorubicin.
    • In the phase III European Organization for Research and Treatment of Cancer (EORTC) 62012 trial, intensified doxorubicin + ifosfamide was shown to have superior median PFS (7.4 vs 4.6 months; P = .002) but similar median OS (14.3 vs 12.8 months; P = .76) compared with doxorubicin alone for patients with soft tissue sarcoma.
  • However, olaratumab, a monoclonal antibody directed against platelet-derived growth factor receptor alpha (PDGFRα) earned accelerated approved by the FDA in October 2016 for the treatment of soft tissue sarcoma in combination with doxorubicin, based on data from a randomized phase II trial in which median PFS showed modest improvement with the combination compared with doxorubicin alone (6.6 vs 4.1 months; P = .0615) but median OS was more impressive (26.5 vs 14.7 months; P = .0003). A phase III trial is ongoing to confirm the benefit of this combination for patients with advanced or metastatic soft tissue sarcoma.
  • Other agents of interest in the first-line management of soft tissue sarcoma include the cyclin dependent kinase 4 (CDK4) inhibitor palbociclib and the albumin-binding anthracycline aldoxorubicin.

For additional commentary about this topic and the Moving Forward From the Status Quo for the Treatment of Soft Tissue Sarcoma: Key Questions and New Answers to Optimize Outcomes symposium, please visit www.gotoper.com.


2 of 3
PER Pulse™ Recap

The live continuing medical education activity, Moving Forward From the Status Quo for the Treatment of Soft Tissue Sarcoma: Key Questions and New Answers to Optimize Outcomes, held adjunct to an annual oncology meeting in Chicago, Illinois, featured the following experts discussing the latest clinical research on soft tissue sarcomas: George D. Demetri, MD; Robin L. Jones, BSc, MB, MRCP, MD (Res); William D. Tap, MD; and Sandra P. D’Angelo, MD. This program featured exciting lectures on cutting-edge research impacting the management of patients with these diseases. The second of 3 PER Pulse™ Recaps discusses the data available to inform treatment decisions for recurrent soft tissue sarcomas.

Below are some highlights from Dr Jones’ lecture:

  • Soft tissue sarcomas are comprised of dozens of distinct subtypes, which often have distinct treatment regimens.
    • For example, gastrointestinal stromal tumor (GIST) is treated with imatinib and other tyrosine kinase inhibitors (sunitinib and regorafenib); giant cell tumor of the bone is treated with denosumab; endometrial stromal sarcoma with aromatase inhibitors, and alveolar soft part sarcoma with angiogenesis inhibitors.
  • Nonetheless, conventional therapy for recurrent soft tissue sarcoma (unspecified subtypes) is primarily single-agent or combination chemotherapy.
    • In a randomized phase II trial of previously treated soft tissue sarcoma, the addition of gemcitabine to dacarbazine produced both a 2.2-month progression-free survival (PFS) advantage (P = .005) and an 8.6-month overall survival (OS) advantage (P = .014).
    • Trabectedin trials have demonstrated superior outcomes of trabectedin compared with best supportive care and dacarbazine in recurrent disease.
    • Two phase III trials of eribulin vs dacarbazine demonstrated a significant survival advantage with eribulin, with 1 trial showing a 2-month OS benefit (P = .0169) among patients with recurrent advanced liposarcoma or leiomyosarcoma, and the other showing a 7.2-month OS benefit among patients with liposarcoma (P = .0006).
  • However, pazopanib, a multikinase angiogenesis inhibitor, demonstrated in the placebo-controlled PALETTE trial that pazopanib produced a significant PFS benefit (hazard ratio [HR], 0.31; P < .0001), earning FDA approval in 2012 for advanced soft tissue sarcoma that had already been treated with chemotherapy.
  • Agents in development for the treatment of recurrent sarcomas include CDK4/MDM2 inhibitors (for well- and dedifferentiated liposarcomas), EZH2 inhibitors (for INI1-negative sarcomas), IDH1 inhibitors (for chondrosarcomas), KIT/PDGFR inhibitors (for GIST), aldoxorubicin, and PD-1/PD-L1 inhibitors.
  • The optimal sequence of agents to be used in the recurrent sarcoma setting has not yet been established.

For additional commentary about this topic and the Moving Forward From the Status Quo for the Treatment of Soft Tissue Sarcoma: Key Questions and New Answers to Optimize Outcomes symposium, please visit www.gotoper.com.


3 of 3
PER Pulse™ Recap

The live continuing medical education activity, Moving Forward From the Status Quo for the Treatment of Soft Tissue Sarcoma: Key Questions and New Answers to Optimize Outcomes, held adjunct to an annual oncology meeting in Chicago, Illinois, featured the following experts discussing the latest clinical research on soft tissue sarcomas: George D. Demetri, MD; Robin L. Jones, BSc, MB, MRCP, MD (Res); William D. Tap, MD; and Sandra P. D’Angelo, MD. This program featured exciting lectures on cutting-edge research impacting the management of patients with these diseases. The third of 3 PER Pulse™ Recaps describes the evolving data in immunotherapy for soft tissue sarcomas.

Below are some highlights from Dr D’Angelo’s lecture:
  • There are 3 main areas of immunotherapy under investigation for the treatment of soft tissue sarcoma: checkpoint inhibition, adoptive T-cell therapy, and vaccines.
    • The SARC028 trial of the checkpoint inhibitor pembrolizumab showed that, of the various soft tissue sarcoma subtypes tested, responses were seen in undifferentiated pleomorphic sarcomas, dedifferentiated liposarcoma, and synovial sarcoma. Moreover, PD-L1 expression was not required for tumor cells to respond to pembrolizumab.
    • In the phase II Alliance A091401 trial, combination checkpoint inhibition using nivolumab + ipilimumab produced responses in a variety of sarcoma subtypes, with a 16% response rate overall and a 1-year survival rate of 55%.
    • NY-ESO-1 is a cancer testis antigen highly expressed on the majority of T cells in certain sarcoma subtypes, making it an attractive therapeutic target. T cells engineered for their receptors to recognize an NY-ESO-1-derived peptide are under investigation as adoptive T-cell therapy, where it appears that both high and low NY-ESO-1-expressing tumors can respond to treatment.
    • CMB305 is a combination immunotherapeutic product comprised of a dendritic vaccine and an engineered vector containing nucleic acids encoding the NY-ESO-1 antigen. In a first-in-human study of CMB305, 64% of the 25 evaluable patients with soft tissue sarcoma had stable disease.

For additional commentary about this topic and the Moving Forward From the Status Quo for the Treatment of Soft Tissue Sarcoma: Key Questions and New Answers to Optimize Outcomes symposium, please visit www.gotoper.com.







Become a Member

Forgot Password?
Calendar of Events
SUNMONTUESWEDTHURSFRISAT
     12
3456789
10111213141516
17181920212223
24252627282930
31
Filter By