(P 432) THE ROLE OF SYSTEMIC TREATMENT IN ADVANCED SOLITARY FIBROUS TUMORS: EXPERIENCE AT A REFERRAL CENTER.

Objective: Solitary fibrous tumors (SFT) are rare fibroblastic mesenchymal neoplasms with unpredictable clinical behavior. Surgical resection is the standard treatment for localized disease; however, data regarding optimal systemic treatment strategy for advanced or unresectable SFT are lacking, and therapeutic approaches are heterogeneous. Standard chemotherapy has shown limited efficacy, and other systemic therapies such as antiangiogenics have demonstrated only modest response rates. Limited data have suggested promising activity with the combination therapy of temozolomide/bevacizumab (TZ/BV), but the rarity of this tumor subtype limits the development of large, randomized trials. We aimed to report the efficacy of systemic treatment in our population, particularly TZ/BV, also in heavily pre-treated patients (pts).

Methods: We performed a retrospective analysis of patients with a histopathologically confirmed diagnosis of advanced SFT who were treated with systemic therapy at our center between 2011 and 2024. Patients were categorized as low, intermediate, or high-risk SFT according to the Demicco risk assessment model. Best tumor response to each treatment line was evaluated according to radiologic Choi criteria and classified as partial response (PR), stable disease (SD), or progressive disease (PD). Response rates and Progression-Free Survival (PFS) were reported for each treatment strategy. Due to considerable tumor and treatment heterogeneity, responses to second and subsequent lines of therapy were also assessed using the Growth Modulation Index (GMI), defined as the ratio of PFS with the nth line of treatment to the Time To Progression (TTP) with the n-1th line. A threshold of GMI ≥1.33 indicates meaningful activity and significant overall survival (OS) improvement.

Results: Among 16 SFT pts treated with systemic therapy (mean age 59 [range 48-75], female 81%, low-risk 8 pts [50%], intermediate-risk 5 pts [31%] and high-risk 3 pts [19%]), with a median follow-up of 24 m, median OS was not reached. The most frequently used 1st-line treatment was pazopanib in 8 pts (50%). Of these, 7 were evaluable for response, achieving SD in 3 pts (42,8%), and no PR. Median PFS with 1st-line pazopanib was 7 months (m) (7-12). Other 1st-line therapies were anthracyclin-based regimens: doxorubicin/dacarbazine in 3 pts (18.7%), doxorubicin monotherapy in 2 pts (12.5%) and adriamicine/olaratumab in one patient. Median PFS with 1st-line anthracyclin-based therapy was 5 m (2 – 10). One patient received 1st-line TZ/BV, achieving PR with a TTP of 47 m. Trabectedin and gemcitabine/docetaxel were also given as 1st line in one patient each, both with PD as the best response.
Eight patients (50%) received ≥2 lines of therapy. For second and subsequent lines, median GMI was as follows: 0,41 (0.12-1.9), GMI ≥1.33 in 1 of 4 pts for pazopanib; 1.25 (0.4-3.7), GMI ≥1.33 in 2 of 4 pts for gemcitabine-dacarbazine; 3.67 (0.44-12.84), GMI ≥1.33 in 3 of 4 pts for TZ/BV (although the only patient with GMI < 1.33 is still on treatment and non-progressive at the time of analysis). Doxorubicin monotherapy (GMI 0.75 [0.5-1]) and trabectedin (GMI 0.95 [0.8-1.09]), apparently did not display clinically meaningful activity in 2nd or subsequent lines, although one patient in each group with GMI< 1.33 are still on treatment and non-progressive at the time of analysis.
All patients (5 pts [1 as 1st line, 1 as 2nd, 1 as 3rd, 1 as 4th, and 1 as 5th]) who received TZ/BV presented PR as the best response. Only one patient presented G3/4 toxicity (G3 thrombocytopenia).

Conclusion: This retrospective study suggests that systemic treatment could have more activity in advanced SFT than previously reported. Particularly, the combination treatment TZ/BV demonstrated high response rates and extended progression-free intervals in our population, including heavily pre-treated patients, with no significant toxicity. These findings provide a potential rationale for the earlier use of this treatment strategy in patients with SFT.