Anti-Angiogenic Agents in Management of Sarcoma Patients: Overview of Published Trials

Abstract

We reviewed all fully published clinical trials assessing anti-angiogenic agents in sarcoma patients (last issue, January 13, 2020). Anti-angiogenic macromolecules (e.g., bevacizumab or ombrabulin) provide disappointing results. Many multikinase inhibitors have been assessed with non-randomized phase II trials with limited samples and without stratification according to histological subtypes, therefore interpretation of such trials is very challenging. On the contrary, pazopanib, regorafenib, and sorafenib have been assessed using double-blind placebo-controlled randomized phase II or phase III trials. Compared to placebo, sorafenib demonstrates activity in desmoid-type fibromatosis patients. Based on results of phase 3 trial, pazopanib had obtained approval for treatment of pretreated non-adipocytic soft tissue sarcoma. Regorafenib is currently assessed in several clinical settings and provides significant improvement of progression-free survival in pre-treated non-adipocytic soft tissue sarcoma and in advanced pretreated osteosarcoma. Multikinase inhibitors are a breakthrough in sarcoma management. Many trials are ongoing. Nevertheless, predictive factors are still missing.

Current molecular and therapeutic advances in liposarcoma, rhabdomyosarcoma, leiomyosarcoma, synovial sarcoma, and angiosarcoma

“…In the rat model with leiomyosarcoma, the Aurka inhibitor MK5108 showed a decrease in tumor growth, induction and apoptosis in G2 / M cell cycle arrest and was pro mising with a phase I clinical trial. 10,31…”

“…This study may shed light on promising studies with the idea that it provides dual inhibition of type II leiomyosarcoma subtype showing both mTOR and AurKA over-expression. 10 Like many sarcoma types, ROR2 has been over-expressed in leiomyosarcoma, which it has been activated by Wnt5A in the non-canonical Wnt pathway and strong ROR2 staining has been reported to be associated with poor prognosis in patients with leiomyosarcoma. It has been found that Wnt pathway inhibitors such as OTSA101, an anti-Fzd10 antibody of the over-expressed type II leiomyosarcoma subtype, may be effective.…”

Atezolizumab with bevacizumab, paclitaxel and carboplatin was effective for patients with SMARCA4-deficient thoracic sarcoma

“…The synergistic effects of anti-angiogenic agents and anti-PD-1/PD-L1 antibodies have also been demonstrated [12,13]. The efficacy of anti-angiogenic agents against sarcomas has not been established, but some Phase II trials have shown their efficacy [14]. These combination therapies are expected to be effective for SMARCA4-DTS.…”

Clinical Benefit from Lenvatinib and Pembrolizumab Observed in Mullerian Adenosarcoma: A Case Report

“…Lenvatinib/pembrolizumab is active in metastatic or unresectable endometrial adenocarcinoma, despite low prevalence of PD-L1 expression [ 5 ] and regardless of MMR protein status [ 6 ]. Although our patient’s tumor did not have any adenocarcinoma component, given the lack of standard therapeutic options and the absence of any suitable clinical trial in our institution, this regimen was offered to her on the basis of the known sensitivity of various sarcomas to antiangiogenic tyrosine kinase inhibitors [ 7 , 8 ] and of the synergy observed between the latter and immune checkpoint inhibitors [ 9 ]. This regimen has not been specifically studied in gynecological sarcomas to our knowledge.…”