Ongoing Research Explores Novel Approaches in Soft Tissue Sarcoma

Albert J. Aboulafia, MD, discusses advances in tenosynovial giant cell tumor and the early research and challenges in soft tissue sarcoma treatment.

Albert J. Aboulafia, MD

Treatment advances for patients with tenosynovial giant cell tumor (TGCT) as well as soft tissue sarcoma have remained quiet over recent years; however, a recent approval and preliminary research in phase I studies, respectively, have potential to push the fields forward, explained Albert J. Aboulafia, MD.

“Right now, the clinical landscape for chemotherapy for bone tumors hasn't changed tremendously. For primary malignant bone tumors—the three most common being osteosarcoma, Ewing sarcoma, and chondrosarcoma—the therapeutic options haven’t changed [much],” said Aboulafia. “To date, there is no effective chemotherapy for chondrosarcomas. Additionally, the treatment for Ewing sarcoma and osteosarcoma hasn't changed dramatically.”

The phase II National Cancer Institute (NCI)-MATCH trial continues to look at targeted therapies for patients whose tumors have specific molecular abnormalities across all tumor types.1 In the study, researchers use a DNA sequencing test to identify up to 143 gene mutations in a patient’s tumor that can be targeted by one of the drugs in the trial. Additionally, early-phase studies are looking at targeted therapies in soft tissue sarcoma, he added.

In TGCT, the FDA granted an approval to pexidartinib (Turalio) for the treatment of these patients, based on findings from the placebo-controlled, phase III ENLIVEN trial. Results showed that pexidartinib elicited a 39% (95% CI, 27%-53%) overall response rate with pexidartinib compared with 0% (95% CI, 0%-6%; P <.0001) with placebo following 25 weeks of treatment based on central review of MRI scans.2,3

In an interview with OncLive® during the 2019 Musculoskeletal Tumor Society Annual Meeting, Aboulafia, medical director of the Weinberg Cancer Institute at MedStar Franklin Square Medical Center, discussed advances in TGCT and the early research and challenges in soft tissue sarcoma treatment.

OncLive: Could you discuss some of the recent advances in TGCT treatment?

Aboulafia: TGCT encompasses a variety of diseases. One is outside the joint, which is usually along tendon sheath. In what was previously referred to as pigmented villonodular synovitis (PVNS), there are diffuse forms, as well as nodular or localized forms. The diffuse form is particularly challenging because patients frequently require multiple surgeries. Some people undergo radiation treatments, [although those] have not been terribly effective.

One of the drugs that has been used is imatinib (Gleevec). More recently, a new drug has come on the market; it received FDA approval and is called pexidartinib (Turalio)—a CSF1R targeted therapy. The approval was based on findings from a trial of 120 patients and the response rate [was 39%], with about 15% of patients having a complete response. As soon as that drug got approved, I went through my list of patients with diffuse PVNS because, sooner or later, I suspect many of them will need to look at this as a potential therapeutic intervention.

Are there any other agents that show promise in this field?

Since we do understand the translocation that's most commonly associated with Ewing sarcoma, there are efforts to try and target that translocation in that pathway, but it's relatively complex. We haven't seen the advantages that we have seen in some of the other tumor types, solid tumor types in particular. With soft tissue sarcoma, not much has changed in the last 20 years. There is a single TKI that is approved for patients who have progressed with systemic disease after failing first-line therapy.

What precision medicine efforts, if any, are being made in this disease?

There are not very many. There is a phase I clinical trial looking at targeted therapies, which is probably the most that we are doing. Sarcomas are very heterogeneous groups of diseases. Soft tissue sarcomas in particular, like synovial sarcoma, myxoid liposarcoma, and alveolar rhabdomyosarcoma, do have translocation or molecular rearrangements that we're aware of. It's a very small number of patients who have a targeted mutation, but clinical trials through the NCI and the NCI-MATCH trial show that if you do molecular profiling and you see an NTRK fusion, then you can treat that patient with NTRK-targeted therapy. It's not the sarcoma or the tumor type; it's the mutation specifically that you're targeting.


  1. NCI-MATCH precision medicine clinical trial releases new findings, strengthens path forward for targeted cancer therapies [news release]. Bethesda, MD: National Cancer Institute; June 4, 2018. Accessed October 24, 2019.
  2. Tap WD, Gelderblom H, Stacchiotti S, et al. Final results of ENLIVEN: a global, double-blind, randomized, placebo-controlled, phase 3 study of pexidartinib in advanced tenosynovial giant cell tumor (TGCT). J Clin Oncol. 2018;36(15 suppl; abstr 11502). doi: 10.1200/JCO.2018.36.15_suppl.1150
  3. Tap WD, Gelderblom H, Palmerini E, et al; ENLIVEN Investigators. Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial. Lancet. 2019;394(10197):478-487. doi: 10.1016/S0140-6736(19)30764-0.