(P 031) PAZOPANIB IN ADVANCED BONE SARCOMA: A RETROSPECTIVE ANALYSIS OF RIZZOLI ORTHOPEDIC INSTITUTE

Objective: Osteosarcoma, Ewing sarcoma and Chondrosarcoma are most frequent primary bone sarcoma. Treatment options for advanced bone sarcoma are limited. Prospective phase studies with tyrosine kinase inhibitors (TKIs) have shown activity of these agents and TKIs have been employed more frequently in these advanced patients. In advanced osteosarcoma a median progression free survival (PFS) ranging from 3.4 to 6.2 months was obtained with different TKIs employed (Duffaud F 2020). In Ewing sarcoma series a median PFS ranged from 3,6 months with Regorafenib (Attia S 2017) to 4,4 ms with Cabozantinib (Italiano A 2022). Pazopanib (PZP) is multi TKI approved for treatment of soft tissue sarcoma. A 68% of clinical benefit and a median PFS of 5,4 ms was recently reported with PZP in a series which included several bone sarcomas (Safwat A. 2020). We reviewed results of all cases of bone sarcoma treated with PZP given as an off label use or within a compassionate program at our center

Methods: A total of 40 patients with metastatic bone sarcoma treated from February 2017 to December 2021 with PZP were reviewed from our archives. Informed consent was obtained and Ethical committee approval as well. Patients with progressive metastatic or advanced disease aged >12 were enrolled in a study with compassionate use of PZP.
Median Progression Free Survival (PFS) and median overall survival (OS) and treatment responses (RECIST1.1) are reported.

Results: 40 pts were evaluable: 30 osteosarcoma, 7 Ewing sarcoma and 3 chondrosarcoma. Male: Female= 28:12, median age 31 (12-63 yrs), median number of previous Chemotherapy lines for advanced disease was 3 (1-5), lung was the most frequent site of metastases and all pts had lung metastases, 21 pts had >1 metastatic site; 14 had 2 metastatic sites, 7 had 3 or more metastatic site, most common metastatic sites beside lungs were Bone (11), Local recurrence (7) Liver(4). Thirtytwo patients died of disease, 2 are lost from follow up,6 are still alive ( 5 osteosarcoma and 1 in chondrosarcoma ).PZP starting dose was 800 mg/d in 28/40 patients (17/28 patients remained on treatment with full dose, dose reduction was necessary in 11/28 cases); in 12 patients PZP was started with a reduced dose due to comorbidities (600 mg in 2 pts, 400 mg in 10 pts ) in the three pediatric patients the starting dose was 400 mg/day. Most common Gr3-4 side effects were: hematologic (in 13/40 cases), pneumothorax (in 5/40 cases), hypertension / arrhythmia (13/40 cases ),one patient had a non fatal brain hemorrhage. Median PFS for all 40 pts was 3,7 ms (95%CI 2.97-5.13) , median Overall Survival was 9,3 ms (95%CI 6,97-12,37) 6 pts are still alive with disease. Subgroup analysis: in the osteosarcoma group (30 pts) median PFS was 3.8 ms (95%CI 3.2-6.1) 4/30 ( 13%) had a partial response and 15 a stable disease with 63,3% (19/30) Disease Control Rate with a median PFS of 6 ms (2-20 ms). In Ewing sarcoma group (7 cases) there were only two stable disease ,the median PFS was 2.1 ms (95%CI 0.47-6) and median OS 8,8 ms (95% CI 0.47-12,3) all pts with Ewing sarcoma died; in the 3 chondrosarcoma pts there was 1 Stable Disease ,PFS was 3,7, 3.8, 10.8 ms, one of the three pt is alive

Conclusion: The results of this small retrospective series confirm activity of PZP in advanced osteosarcoma, while its activity in Ewing’s sarcoma patients seems more limited.This information should be taken with caution due to limited number of patients in this serie. Randomized controlled studies comparing PZP with conventional chemotherapy in first or second line after relapse should be undertaken in patients with advanced osteosarcoma. Earlier employ of PZP in advanced bone sarcoma treatment should be evaluated.

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