Active Surveillance Is a Safe and Acceptable Treatment Alternative in Select D-TGCT

Active surveillance may allow patients with diffuse-type tenosynovial giant cell tumor (D-TGCT) without clinical deterioration to avoid surgery or systemic therapies that might be associated with high morbidity or unacceptable risk, according to R. Lor Randall, MD, who emphasized that D-TGCT management requires multidisciplinary conversations between surgical oncologists, medical oncologists, and sarcoma experts, as well as consideration of individual patient treatment goals.

A retrospective, multicenter cohort study pooled data from 61 patients with treatment-naive primary D-TGCT whose disease was initially managed by active surveillance across 8 sarcoma centers worldwide.¹ At a median follow-up of 28 months, 64% of the 58 evaluable patients had no clinical deterioration during follow-up and 36% experienced radiologic progression after a median of 21 months. Furthermore, 18% of patients who did not have osteoarthritis at baseline (n = 45) developed osteoarthritis during follow-up, and 31% of patients required a subsequent treatment.

Currently, pexidartinib (Turalio) is the only-FDA approved CSF1R inhibitor for patients with symptomatic TGCT that is associated with severe functional limitations or mortality and does not improve with surgery.² Although these inhibitors have demonstrated favorable radiologic and clinical outcomes in D-TGCT, their risk-benefit ratio and adverse effect [AE] profile may not be preferred in the case of a benign disease.¹

“If these patients are not showing disease progression and they’re not experiencing symptomatic deterioration, it’s okay to continue to watch them,” Randall said.

In an interview with OncLive^®, Randall discussed how the findings from this study confirm the adequacy of active surveillance for select patients with D-TGCT, available salvage therapies for patients who experience clinical deterioration, and the importance of shared decision making regarding D-TGCT surveillance or treatment.

Randall is the David Linn Endowed Chair for Orthopaedic Surgery, as well as a professor and chair of the Department of Orthopaedic Surgery at The University of California, Davis, in Sacramento.

OncLive: What was the design of this study assessing active surveillance in patients with D-TGCT, and what findings were observed?

Randall: This [study encompassed] a group of sarcoma centers from across the world. Eight centers got together to evaluate our experience with TGCT, which is a nonmalignant condition. I call it a malignant nonmalignancy, meaning it can cause real problems and destruction locally, but it’s not usually multifocal and doesn’t metastasize. TGCT is of interest to the medical oncology community because CSF1R inhibitor therapies are [becoming] available. Medical oncologists are partnering with sarcoma surgeons to treat [patients with] TGCT.

The study primarily [consisted of] surgeons from around the world, including the Netherlands, Italy, and Canada, [as well as] Los Angeles and Sacramento [in California]. We combined our experience with patients with D-TGCT, pooled all our patients who were therapy naive, followed them, and retrospectively investigated how this cohort of patients did.

We [identified] 61 patients between [all centers] with D-TCGT who were managed with active surveillance. Fifty-nine [of these patients] had an MRI performed at baseline. Ninety-five percent of these patients had intra-articular disease, and a few had extra-articular disease. There was a bit of baseline arthritis in some of these patients, and most patients had some symptoms, including pain and swelling. Eight patients, or 13% of patients, were asymptomatic. These patients [had] treatment-naive D-TCGT predominantly in the knee and were followed.

We found that almost two-thirds of the patients [who underwent] active surveillance did not experience clinical deterioration during their follow-up period, which was [a median of] 28 months. Many patients with diffuse-type disease [who exhibited] some symptoms did not [experience any] deterioration in their condition. The flip side is that just over one-third of patients did experience deterioration.

The take-home message is: if a patient has TGCT, you need to listen carefully to how bad their symptoms are. It is not inappropriate to watch these patients for a period of time. If they do have progression or symptomatic deterioration, then the sarcoma experts, [along] with medical oncologists, need to determine whether [these patients] should receive a CSF1R inhibitor or go to surgical intervention. That usually will require a multidisciplinary tumor board.

What salvage therapy might patients with D-TGCT receive at the time of clinical deterioration?

Some of the progression [experienced by patients in the study manifested as] increasing swelling and pain, but there was also progression of osteoarthritic changes; there can be erosive changes in the bone from the disease. Some patients [in the study] might have ultimately needed surgery, such as a total knee [synovectomy]. Other patients, depending upon symptoms, would receive CSF1R inhibition.

The global regions included in the study did not include the East Coast of the United States (US). What might have been the reason for this omission?

I think it was purely happenstance. [This study just included] big [sarcoma] centers in the US. The one [center included in the study from] Canada is in Toronto, so that’s more east in North America. [This study also involved] the Mayo Clinic in Rochester, Minnesota, [which represented] the Midwestern US.

What guidelines recommend the use of active surveillance in patients with TGCT?

The National Comprehensive Cancer Network [recommends that] these lesions should generally be watched before intervention.

Is active surveillance feasible for patients with TGCT receiving treatment at community oncology centers?

[TGCT is an] uncommon enough condition that patients should probably at least undergo an initial evaluation at the equivalent of a sarcoma program or an academic medical center. TGCT is not common enough that community medical oncologists or community orthopedic surgeons will see [patients with this disease] regularly. It’s probably appropriate to [recommend that patients with TGCT] see experts who see this disease in high volume, but the surveillance can continue through the community medical oncologists or surgeons.

What ongoing or planned research in D-TGCT would you like to highlight?

The oral CSF1R inhibitor [pexidartinib] is now commercially available [for patients with D-TGCT], but an ongoing trial [is investigating] an intra-articular version of the drug. This would be nice [to have] because it has a local delivery mechanism.

References

1. Spierenburg G, Staals EL, Palmerini E, et al. Active surveillance of diffuse-type tenosynovial giant cell tumors: A retrospective, multicenter cohort study. Eur J Surg Oncol. 2024;50(2):107953. doi:10.1016/j.ejso.2024.107953
2. FDA approves first therapy for rare joint tumor. FDA. August 2, 2019. Accessed February 14, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-rare-joint-tumor