Pazopanib in metastatic soft tissue sarcoma (STS): Results of a multi-institutional observational study.
Background: Soft tissue sarcomas (STS) are a heterogenous group of tumors which have limited therapeutic options and poor prognosis in advanced/metastatic settings. Herein, we present the clinical outcomes of metastatic STS patients treated with pazopanib (PAZ) in real-life. Methods: We retrospectively collected data about adult patients treated with PAZ for metastatic STS in Turkey. We described the clinical characteristics and tumor responses, and estimated the progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method. The Cox proportional hazards regression model (HR, 95%CI) was used for evaluation of prognostic factors for PFS. Results: 507 patients (median age: 52 [range: 18-87]; 56.8% female) were included in the analysis. Extremities were the most common primary tumor sites (n:202; 39.8%) followed by abdomen (n:116; 22.9%) and pelvic cavity (n:102;20.1%) where 98% of STSs arose in uterus (n:100). The leading histologic subtypes were leiomyosarcoma (n:192; 37.9%), synovial sarcoma (n:58; 11.4%) and undifferentiated pleomorphic sarcoma (n:48; 9.5%). Of the reported tumor grades (n = 350), 61.4% (n:215) were grade 3. The most common metastatic sites were lungs (52.7%) and liver (20.3%). Doxorubicin plus ifosfamide (45.9%) was the preferred front-line regimen and PAZ was the treatment of choice in second (59.8%) and third-line (61.8%) settings. The median follow-up under PAZ treatment was 5.03 (0.10-84.67) months. Objective response and disease control rates were 31.4% and 42.2%, respectively. Overall, 183 (36.1%) patients were alive at last follow up, 123 of which (67.2%) did not show progression. The median PFS and OS for the study group and the most commonly observed types of STS are shown in Table. Favorable prognostic factors for PFS were low-intermediate tumor grade (HR[95% CI] for grade I and 2 vs 3:1.371[1.016-1.849]; p = 0.039) and ECOG (Eastern Cooperative Oncology Group) score (HR[95% CI] for ECOG score < 2 vs ≥2: 2.698[1.923-3.787]; p = 0.0001). Weakness/asthenia (10.8%), impaired liver function tests (4.7%) and diarrhea (3.6%) were the most common adverse events, no grade 4 or 5 events were observed. Conclusions: This large scale real-life study confirms that PAZ, with its positive impact on clinical outcomes and acceptable tolerability and safety profile is a valuable treatment option for metastatic STS.
|Progression free survival*||Overall Survival*|
|Overall (n = 507)||7.070 (5.796-8.344)||12.900 (11.165-14.635)|
|Leiomyosarcoma (n = 192)||6.870 (5.144- 8.596)||13.830 (10.051-17.609)|
|Synovial sarcoma (n = 58)||10.300 (3.305-17.295)||12.270 (10.556-13.984)|
|Undiferentiated pleomorphic sarcoma (n = 48)||7.230 (3.458-11.002)||15.730 (7.542-23.918)|
*Presented as median (months) (95% Confidence Interval).