Jonathan C. Trent,
Updates in sarcoma presented at the 2016 ASCO Annual Meeting highlighted the latest progress with targeted treatments and immunotherapy agents in the field.
For example, findings from the double-blind phase II REGO-SARC trial1—which is comparing the multikinase inhibitor regorafenib (Stivarga) with placebo in pretreated patients with liposarcoma, leiomyosarcoma, synovial sarcoma, and other types of soft tissue sarcoma—showed that 4 partial responses have been observed thus far.
With immunotherapy, results of the multicenter phase II SARC-028 trial2 showed that pembrolizumab (Keytruda) had an overall response rate of 22% in patients with undifferentiated pleomorphic sarcoma.
In an interview with OncLive
, Jonathan C. Trent, MD, PhD, professor of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses these and other notable results that emerged at ASCO, as well as what lies ahead for the field of sarcomas.
OncLive: There were some interesting data presented at the 2016 ASCO Annual Meeting in sarcoma. Can you share the details?
: In one presentation, given by Dr Jeremy Whelan, on the EURO-EWING 99-R2 study [abstract 11000], he showed that there was superiority for patients who have high-risk Ewing sarcoma who were treated with stem cell transplant. These patents with high-risk disease had a better overall survival (OS) and progression-free survival (PFS) after transplant compared with patients who were treated with standard cytotoxic chemotherapy.
These data particularly emphasizes the poor outcomes of patients with high-risk Ewing sarcoma. Those patients really need to be evaluated at a sarcoma center that really has the capability of a stem cell transplant in the patient for whom that is indicated.
Ewing sarcoma is one of several sarcoma subtypes. What have been some of the biggest challenges with this one?
Ewing sarcoma is a very rare disease; it’s even a very rare type of sarcoma. There is very limited data in terms of clinical trials in adults, as most of the information that we have is in children. This is such a rare disease that it is difficult to do large studies.
What other recently published data have you found to be exciting in this field?
There were also several abstracts on targeted therapy on sarcomas at the 2016 ASCO Annual Meeting. One study showed that there was a PFS benefit with regorafenib compared with placebo in patients with leiomyosarcoma, liposarcoma, or synovial sarcoma.
The interesting thing about that study is that regorafenib clearly has activity in soft tissue sarcoma. We won’t know, however, whether or not the activity is superior to pazopanib (Votrient) based on this single-arm placebo-controlled study.
What headway are we making in terms of immunotherapy in this field?
In the SARC-028 study, pembrolizumab was used as a single agent in patients with several subtypes of sarcoma. The overall objective response rate was 19%, and the disease-free rate at 4 months was 44% compared with a historical control rate of 20%.
This clearly shows activity with pembrolizumab in patients with pleomorphic sarcoma, well-differentiated liposarcoma, and synovial sarcoma. In a presentation, Dr Breelyn Wilky pointed out that there were several approaches in immunotherapy that can work together with pembrolizumab. The potential follow-up study is her study of pembrolizumab plus axitinib (Inlyta), a multikinase inhibitor, in patients with metastatic soft tissue sarcoma.
Can you provide some insight on the T-cell therapy that has received a breakthrough therapy designation by the FDA?
Cellular therapies are very exciting in all types of cancer, particularly in sarcomas, because of our plethora of neoantigens on the tumor cells. Many types of sarcomas have translocations, point mutations, etc, that lead to novel antigens that can be specifically recognized by an engineered T cell.