Real-World Experiences with Pazopanib in Patients with Advanced Soft Tissue and Bone Sarcoma in Northern California

Abstract

Background: Pazopanib was approved for advanced soft tissue sarcoma as a second- or third-line therapy based on the clinical trial “Pazopanib for metastatic soft-tissue sarcoma” (PALETTE). We hypothesized that the real-world experiences may be significantly different from the clinical trial results. Methods: We analyzed the response pattern of patients with advanced soft tissue and bone sarcoma who received pazopanib treatment between 1 January 2011 and 31 October 2018 in Kaiser Permanente Northern California. Results: A total of 123 patients with 23 different histologic subtypes were assessable. One patient with low-grade fibromyxoid sarcoma obtained complete response (CR) after 2 months of treatment with pazopanib, 12 patients (9.7%) obtained partial response (PR), 34 patients (27.6%) had stable disease (SD), while 76 patients (61.8%) developed progressive disease (PD). The disease control rate (DCR) was 46.3% (CR + PR + SD). Among the 12 patients with PR, 3 had undifferentiated pleomorphic sarcoma (UPS), 4 had leiomyosarcoma (LMS), 2 had pleomorphic rhabdomyosarcoma, 1 had pleomorphic liposarcoma, 1 had dedifferentiated liposarcoma, and 1 had angiosarcoma. The median duration of response was 9 months. Two patients with Ewing’s sarcoma had SD for 6 and 13 months, and two patients with osteosarcoma had SD for 6 and 9 months. Among 65 patients assessed at 8 weeks, 9 had a response, and 10 had SD. Among 104 patients assessed at 12 weeks, 12 had a response, and 26 had SD. The median progression-free survival (PFS) was approximately 3 months for all 123 cases and for patients with UPS and LMS. Conclusions: Our cohort of patients with advanced soft tissue and bone sarcoma in Northern California treated with pazopanib had diverse histologic subtypes. The response rate (CR + PR) was higher than that of the PALETTE trial, while the DCR and the median PFS were significantly lower. The observation of PR in two patients with liposarcoma and durable SD in several patients with bone sarcoma indicates that pazopanib has activity in liposarcoma and bone sarcoma.

Low-grade Fibromyxoid Sarcoma: Treatment Outcomes and Efficacy of Chemotherapy

“…It can cause significant morbidity with a paucity of evidence to guide management in the advanced/metastatic setting. To our knowledge, this single-centre retrospective study of LGFMS is the largest published cohort to date (2,(12)(13)(14)(15)(16)(17)(18)(19)(20). Our data provide a benchmark for future studies of systemic therapy in advanced LGFMS.…”

Molecular Biology of Osteosarcoma

“…The mPFS in the whole group was 5.5 months, ORR 32% and DCR 68%. Efficacy of pazopanib was also shown in some case reports of pediatric [183] and adult patients [184][185][186], with PFS of approximately six months. The available data are unclear, and results need verification in randomized studies.…”

Phase II clinical trial of pazopanib for patients with unresectable or metastatic malignant peripheral nerve sheath tumors

“…Combination use of genetespib, an injectable potent small molecule inhibitor of Hsp90, with sirolimus, an oral mTOR inhibitor, achieved no response in 13 patients with refractory MPNST 33 . Regarding pazopanib, three retrospective studies showed the outcomes for MPNST cases, indicating no PR patients although the numbers of cases were up to 5 34‐36 . Nakamura et al reported that patients with MPNST had a poorer response to pazopanib than other histotypes based on the postmarketing surveillance (PMS) data 34 .…”

“…Regarding pazopanib, three retrospective studies showed the outcomes for MPNST cases, indicating no PR patients although the numbers of cases were up to 5. [34][35][36] Nakamura et al reported that patients with MPNST had a poorer response to pazopanib than other histotypes based on the postmarketing surveillance (PMS) data. 34 Furthermore, the median PFS in patients with MPNST was 7.4 weeks (1.7 months), which was much worse than that in the present study (5.4 months) ( 40 This highlights the present reality in which devising effective second line drug treatment after standard chemotherapy for MPNST remains an urgent task.…”