There are also several types of sarcoma, such as synovial sarcoma and liposarcoma, f express testicular antigens—such as NY-ESO-1—that are not expressed in any other cell in the human body. These neoantigens can be targets of modified T cells, such as the T cells that are now being engineered by a number of different companies to bind to and kill NY-ESO-1 in synovial sarcoma and liposarcoma cells. These clinical trials are available not only at the Sylvester Comprehensive Cancer Center, but at many other centers across the country.
How would you say the field has evolved?
There have been a lot of advances in the treatment of sarcomas recently—mainly for patients with metastatic sarcoma. Trabectedin (Yondelis) was approved not that long ago for patients with liposarcoma or leiomyosarcoma, based on a PFS benefit.
Interestingly, another agent, eribulin (Halaven), has been approved for patients with liposarcoma. There is clear activity in this disease. Something that is being evaluated for a potential FDA approval is a novel agent called olaratumab that has shown superiority in combination with doxorubicin compared with doxorubicin alone in patients with soft tissue sarcoma. That superiority includes an OS benefit.
What can we expect in the near future?
With the approval of several new agents that are active in patients with metastatic sarcoma, the next step will be evaluating combination therapy. We also need to determine ways of optimizing mechanisms of action with non-overlapping toxicities so that we have optimal efficacy, kill tumor cells and, ideally, give patients not only a better quality of life but also, hopefully, a better quantity of life.
Once we find optimal therapies in the metastatic setting, the next leap will be toward those patients with a primary sarcoma. If you look at all comers of patients with primary extremity sarcoma, there is only about a 50% OS rate. Using these newer agents upfront may really enhance our ability to cure these patients who have a primary sarcoma before it can manifest into metastatic disease.
- Penel N, Mir O, Italiano A, et al. Regorafenib (RE) in liposarcomas (LIPO), leiomyosarcomas (LMS), synovial sarcomas (SYN), and other types of soft-tissue sarcomas (OTS): Results of an international, double-blind, randomized, placebo (PL) controlled phase II trial. J Clin Oncol. 2016;34 (suppl; abstr 11003).
- Tawbi HAH, Burgess, MA, Crowley J, et al. Safety and efficacy of PD-1 blockade using pembrolizumab in patients with advanced soft tissue (STS) and bone sarcomas (BS): Results of SARC028—A multicenter phase II study. J Clin Oncol. 2016;34 (suppl; abstr 11006).