Long-term survival of participants in the PASART-1 and PASART-2 trials of neo-adjuvant pazopanib and radiotherapy in soft tissue sarcoma

Objective:This study aims to assess the long-term safety and efficacy of adding pazopanib to neo-adjuvant radiotherapy followed by surgery in patients with high-risk non-metastatic soft tissue sarcoma of the trunk and extremities treated in the PASART-1 and PASART-2 trials, as well as to compare the PASART cohorts to a control cohort receiving standard treatment during the same time period from the Netherlands Cancer Registry (IKNL) to investigate if adding pazopanib improves Overall Survival (OS). Methods: Updated follow-up data on disease control, survival and long-term toxicities of the PASARTtrials were extracted from electronic patient records. The effect of adding pazopanib to neo-adjuvant radiotherapy on OS was investigated by comparing the combined PASART cohorts to the IKNL cohort via direct comparison and exact matching analysis. Results: PASART-trials included 34 patients, IKNL cohort included 487 patients. After a median follow-up of 75.4 months (range: 30-131 months) the 1-year, 2-year and 5-year OS in the PASART-trials were 97% (95% confidence interval [CI]: 91.5-100), 85.3%(95%CI: 74.2-98.1), 79.3%(95%CI: 66.8-94.2), respectively. Matching resulted in 23 PASART and 89 IKNL patients. Adding pazopanib did not significantly improve OS when compared to standard treatment (IKNL) in a direct comparison (hazard ratio [HR]: 0.58; 95% CI: 0.30-1.13) or matched analysis (HR: 0.70; 95%CI: 0.29-1.73). Long-term toxicities, mainly fibrosis (n = 6) and edema (n = 2), were observed in 11 PASART patients and comparable to historical controls. Interpretation: The addition of pazopanib had tolerable long-term toxicity but did not improve OS when compared to a control cohort receiving standard treatment.