Pazopanib in rare histologies of metastatic soft tissue sarcoma

Abstract

Background: Uncommon histopathological subtypes account for less than 5% cases of soft tissue sarcoma (STS) and unclassified STSs comprise another 16%, these are often chemotherapy-resistant, with a dismal outcome in unresectable/metastatic disease. Prospective studies on the use of pazopanib in this cohort of patients are lacking in the literature. Here, we describe the safety and efficacy of pazopanib in rare histologies of advanced STS. Materials and methods:We conducted a retrospective study at two tertiary cancer centres in India, evaluating 33 cases of rare subtypes of STS, who received pazopanib as per institutional protocol between January 2013 and December 2019. Patients who received pazopanib for unresectable/metastatic disease were enrolled in this study for clinicopathologic features, treatment outcome and evaluation of prognostic factors.Results: Out of 33 patients, there were seven cases of undifferentiated pleomorphic sarcoma, four cases each of myxofibrosarcoma, epithelioid sarcoma and malignant peripheral nerve sheath tumour, three cases each of haemangiopericytoma and spindle cell sarcoma, two cases of haemangioendothelioma and a case each of clear cell sarcoma, retroperitoneal sarcoma, angiosarcoma and pleomorphic rhabdomyosarcoma-adult type. The objective response rate was 27%. Most of the patients (67%) received pazopanib in second or subsequent lines of therapy. The majority (70%) were started at a lower dose of 400/600 mg and only 43% of these (10/23) could be escalated to a full dose of 800 mg based on tolerance. On univariate analysis, pazopanib's starting dose didn't predict progression-free survival (PFS)/overall survival (OS)/response rate. At a median duration of follow-up of 18.8 months (range 1.9-150.4 months), the median PFS and median OS were 10.3 months (95% confidence interval (CI): 5.9-14.8) and 17.8 months (95% CI: 10.7-29.3), respectively. 27% of the patients experienced grade ¾ toxicities, 12% required dose modification of pazopanib and 21% needed permanent discontinuation due to toxicity. Conclusion:Our study shows that pazopanib is active in rare subtypes of STS.

PAK1 overexpression promotes myxofibrosarcoma angiogenesis through STAT5B-mediated CSF2 transactivation: clinical and therapeutic relevance of amplification and nuclear entry

“…Notably, the PAK1/CSF2 pro-angiogenic axis is not mechanistically linked to the VEGF and VEGF-C. Nevertheless, this result does not completely exclude the possibility of VEGF inhibitors as a therapeutic strategy in myxofibrosarcomas, although pazopanib, a multi-kinase inhibitor also curbing VEGF-VEGFR axis, only showed limited efficacy [52]. Moreover, no prospective randomized clinical trials have systematically assessed the effect of VEGF inhibition in myxofibrosarcomas.…”

Metastatic clear cell sarcoma of the pancreas: A rare case report

“…According to the literature, chemotherapy and radiotherapy for CCS are unsatisfactory[ 19 - 22 ]. Some studies have demonstrated that targeted therapy or immunotherapy may be effective; however, no confirmatory clinical trials have been conducted[ 23 - 27 ].…”

Biology and Management of High-Grade Myxofibrosarcoma: State of the Art and Future Perspectives

“…Although limited by the small number of patients, there are several retrospective studies concerning the role of pazopanib treatment for advanced MFS [94,95]. A Japanese musculoskeletal oncology group study showed that, out of eight MFS patients, four (50%) had stable disease (SD), two (25%) had long SD, and two (25%) had progressive disease (PD) [94].…”

“…A Japanese musculoskeletal oncology group study showed that, out of eight MFS patients, four (50%) had stable disease (SD), two (25%) had long SD, and two (25%) had progressive disease (PD) [94]. In the Indian retrospective study, Kataria et al reported that, out of four MFS patients, two (50%) had SD and two (50%) had PD [95]. More recently, a prospective multicenter phase 2 trial (NCT02575066, acronym PASART-2) was performed to investigate the efficacy of neo-adjuvant pazopanib and concurrent external beam radiotherapy for high-risk, localized STS [96].…”