Pazopanib in advanced or metastatic synovial sarcoma: The Gustave Roussy experience

Background: Synovial sarcoma (SS) is a rare malignancy usually considered as sensitive to chemotherapy (CT) based on anthracyclins and ifosfamide. Therapeutic options are limited and prognosis of advanced or metastatic SS (a/mSS) remains dismal. Since approval of pazopanib in advanced soft tissue sarcomas (STS), very few data were reported on the activity of pazopanib in a/mSS. Methods: We retrospectively reviewed all patients (pts) treated with pazopanib for a/mSS in our institution. The histological diagnosis was confirmed by a referral pathologist within the French Sarcoma Group. Data were obtained from medical records. Radiological response was assessed by CT-scan according to RECIST 1.1. Adverse events were graded according to the Common Terminology Criteria for Adverse Events of the National Cancer Institute 4.03. The aim of this study was to evaluate the activity of pazopanib in a/mSS. Results: From December 2006 to April 2018, 16 pts with a/mSS of extremities (10 pts), trunk (5 pts) or head and neck region (1 patient) were treated with pazopanib from 400 mg to 800 mg daily dose. Median age was 40 years old (range: 24-69). Pts received a median of 2 prior lines of doxorubicin-based CT in all but one case. Thirty-one per cent of pts received pazopanib in 2nd line therapy and 69% in subsequent lines. Before treatment, 15 pts (94%) had distant metastases (lung in 94%, bone in 25%, associated with local recurrence in 20%) and 1 patient (6%) had unresectable local recurrence. A clinical benefit was observed in 87.5% of pts: 7 (43%) experienced a partial response and 7 (43%) a stable disease. Two pts progressed rapidly during treatment. Two pts definitively interrupted pazopanib due to grade 3 sepsis or hemoptysia. The dose was reduced for 2 pts due to diarrhea and hematuria. On April 2018, 6 patients were still on treatment. The median progression free survival (mPFS) was 6.5 months (1-17+). After a median follow-up of 8.5 months, the median overall survival was not reached. Conclusions: Pazopanib showed significant clinical activity in a/mSS along with manageable toxicity profile. We observed a prolonged mPFS compared with other subtypes of STS. These results need to be confirmed in prospective trials dedicated to this histological subtype of STS. Legal entity responsible for the study: Institut Gustave Roussy. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.