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Published on: July 17, 2013
Anti-Angiogenic Agents in Management of Sarcoma Patients: Overview of Published Trials
Pierre-Yves Cren1, Loïc Lebellec1,2, Thomas Ryckewaert3
1Lille University, Medical School, Lille, France.
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.
Insights
Multikinase inhibitors show promise in sarcoma treatment, with pazopanib and regorafenib demonstrating efficacy in specific subtypes. Further research is needed to identify predictive factors for these anti-angiogenic agents.
Area of Science:
- Oncology
- Pharmacology
Background:
- Anti-angiogenic agents are being investigated for sarcoma treatment.
- Macromolecular anti-angiogenic agents have shown limited efficacy.
- Multikinase inhibitors (MKIs) represent a promising class of agents.
Purpose of the Study:
- To review clinical trials of anti-angiogenic agents in sarcoma patients.
- To evaluate the efficacy and safety of MKIs in various sarcoma subtypes.
- To identify the current status and future directions of anti-angiogenic therapy in sarcoma.
Main Methods:
- Systematic review of fully published clinical trials up to January 13, 2020.
- Focus on randomized controlled trials (RCTs), particularly double-blind, placebo-controlled studies.
- Analysis of data from phase II and phase III trials assessing MKIs like pazopanib, regorafenib, and sorafenib.
Main Results:
- Bevacizumab and ombrabulin (macromolecules) yielded disappointing results.
- Sorafenib showed activity in desmoid-type fibromatosis compared to placebo.
- Pazopanib is approved for pretreated non-adipocytic soft tissue sarcoma.
- Regorafenib improved progression-free survival in pretreated non-adipocytic soft tissue sarcoma and advanced osteosarcoma.
Conclusions:
- Multikinase inhibitors are a breakthrough in sarcoma management.
- Pazopanib, regorafenib, and sorafenib have demonstrated clinical activity in specific sarcoma types.
- Ongoing trials are expanding the use of MKIs, but predictive factors are still lacking.
