Poor Treatment Outcomes with Second-Line Chemotherapy in Advanced Synovial Sarcoma

Abstract

Introduction: Synovial sarcoma predominantly affects adolescents and young adults. Doxorubicin with or without ifosfamide therapy is the standard first-line treatment for unresectable or metastatic synovial sarcoma. However, there is no standard second-line chemotherapy regimen. The purpose of the current study was to evaluate the outcomes of second-line chemotherapy for patients with synovial sarcoma. Methods: We retrospectively evaluated the outcomes of 61 patients with unresectable or metastatic synovial sarcoma who had received first-line chemotherapy at our institution between 1997 and 2017. Patients who received second-line chemotherapy were included in the analysis. Outcomes of the chemotherapy were evaluated. Results: Among the 61 patients treated with first-line chemotherapy, we identified 32 patients who received second-line chemotherapy. Most patients (62.5%) were under 40 years of age. Regarding second-line chemotherapy regimens, 6 (18.8%) patients were treated with doxorubicin with/without ifosfamide, 6 (18.8%) with ifosfamide and etoposide, 4 (12.5%) with docetaxel and gemcitabine, 5 (15.6%) with pazopanib, 2 (6.2%) with trabectedin, and 1 (3.1%) with eribulin. The overall response rate according to the Response Evaluation Criteria in Solid Tumors for all patients was 9.4%. Eleven patients (34.3%) achieved disease-control for > 6 months. The median follow-up duration was 15.2 months. The 1-year progression-free and overall survival rates were 33.1% and 67.1%, respectively. Conclusion: Our exploratory study revealed that the response rate of second-line chemotherapy regimens for patients with synovial sarcoma was 9.4%. Therefore, there is an urgent need to develop more active therapeutic regimens for synovial sarcomas.

Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in Synovial Sarcoma

“…DOX-based chemotherapy remains the commonly practiced standard therapy in many centers, and adding IFO to DOX increases overall response rates and progression-free survival, but neither significantly extend overall survival (Edmonson et al, 2003; Judson et al ., 2014). Pazopanib is a pan-kinase inhibitor approved for SS but has a low response rate (Kojima et al, 2022; Yoo et al, 2015). Merck’s PD-1 inhibitor, Pembrolizumab, was recently evaluated in soft tissue sarcomas including 10 SS cases with only one patient having a response (Tawbi et al, 2017).…”

Chemotherapeutic drugs for soft tissue sarcomas: a review

“…To date, doxorubicin remains the first-line chemotherapeutic drug for STSs ( Cojocaru et al, 2022 ; de Juan Ferre et al, 2021 ; von Mehren et al, 2020 ; Smrke et al, 2020 ; Smolle et al, 2020 ; Meyer and Seetharam, 2019 ; Yang et al, 2022 ; Gronchi et al, 2017 ). Selecting second- or higher-line drugs for advanced STS remains a challenge ( Frezza et al, 2017 ; Kim et al, 2019 ; Haddox and Riedel, 2020 ; Younger et al, 2021 ; Kojima et al, 2022 ).…”