Jonathan C. Trent, MD, PhD, professor and associate director for Clinical Research at the Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the need to develop novel combination strategies for the treatment of patients with metastatic gastrointestinal stromal tumors (GIST). 

Currently, the main therapeutic advances that have been made for patients with metastatic GIST include improved KIT inhibitors and PDGFRA inhibitors, says Trent. However, in order to push the field forward, novel combination strategies with different mechanisms of action and non-overlapping toxicities are needed, Trent explains. 

For example, therapies that target BCL-2 through a BH3 mimetic or autophagy inhibitors, such as hydroxychloroquine (Plaquenil) or similar agents, could have utility in combination regimens, Trent concludes.

Videos

Jonathan C. Trent, MD, PhD, discusses the need to develop novel combination strategies for the treatment of patients with metastatic gastrointestinal stromal tumors.  



Dr. Trent on the Need for Novel Combination Strategies in Metastatic GIST 

Jonathan C. Trent, MD, PhD, professor and associate director for Clinical Research at the Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the role of adjuvant imatinib (Gleevec) in gastrointestinal stromal tumors (GIST).

 Surgery is the mainstay of treatment for patients with a primary GIST; however, surgery alone is not always effective, explains Trent. Notably, about 50% of patients will experience disease recurrence after surgery. Oftentimes, these recurrences occur as metastatic disease, Trent says.

Over the years, a number of trials emerged that provided the space with greater insight, including a study that evaluated 2 years of adjuvant imatinib, says Trent. Results of the study showed that adjuvant imatinib was more effective versus no adjuvant therapy. More recently, a phase 3 study from the Scandinavian Sarcoma Group (NCT00116935) demonstrated that 3 years of imatinib after surgery can increase progression-free survival and overall survival compared with 1 year of imatinib in patients with GIST. As such, when treating patients with high-risk GIST, adjuvant therapy with imatinib is now the standard of care. Additionally, neoadjuvant therapy is often implemented as a means to decrease tumor size and allow for organ-sparing surgery, Trent concludes.

Jonathan C. Trent, MD, PhD, discusses the role of adjuvant imatinib in gastrointestinal stromal tumors. 


Dr. Trent on the Role of Adjuvant Imatinib in GIST 

Jonathan C. Trent, MD, PhD, professor and associate director for Clinical Research at the Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the role of circulating tumor DNA (ctDNA) in soft tissue sarcoma. 

ctDNA could ​play an important role in terms of therapy selection following imatinib (Gleevec) resistance, says Trent. 

For example, patients with secondary-resistant, 

 exon 13​–mutant gastrointestinal stromal tumors (GISTs) seem to be sensitive to sunitinib (Sutent), despite being resistant to other TKIs. 

 exon 17–mutant GIST​s who are resistant to imatinib seem to be resistant to sunitinib but sensitive to other TKIs, Trent concludes. 

Jonathan C. Trent, MD, PhD, discusses the role of circulating tumor DNA in soft tissue sarcoma. 

Dr. Trent on the Role of ctDNA in Soft Tissue Sarcoma 

Jonathan C. Trent, MD, associate director for Clinical Research, director of the Sarcoma Medical Research Program at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, discusses sequencing trabectedin (Yondelis) for patients with soft tissue sarcoma.

The phase III ET743-SAR-3007 study led to the FDA approval in October 2015 of trabectedin for patients with leiomyosarcoma and liposarcoma who were previously treated with chemotherapy that included an anthracycline. Previous data have shown that trabectedin demonstrates activity in myxoid liposarcoma, in which second-line therapy with gemcitabine/docetaxel has not proven to be effective, Trent says.

In clinical practice, Trent explains that he would administer trabectedin to patients who were resistant to doxorubicin plus a phosphamide with a 24-hour infusion every 3 weeks. For patients with leiomyosarcoma who are sensitive to doxorubicin plus a phosphamide, Trent suggests they can be treated with gemcitabine/docetaxel as a second-line therapy. Trabectedin could be given in the third-line setting for metastatic disease, he adds.

A clinical trial comparing the efficacy of gemcitabine/docetaxel with trabectedin would determine which therapy may be more beneficial for patients, Trent explains. 

Jonathan C. Trent, MD, associate director for Clinical Research, director of the Sarcoma Medical Research Program at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, discusses sequencing trabectedin (Yondelis) for patients with soft tissue sarcoma.


Jonathan C. Trent, MD

Articles

Dr. Trent on the Need for Novel Combination Strategies in Metastatic GIST

Dr. Trent on the Role of Adjuvant Imatinib in GIST

Dr. Trent on the Role of ctDNA in Soft Tissue Sarcoma

Dr. Trent on Sequencing Trabectedin for Patients With Soft Tissue Sarcoma