Abstract
BackgroundPatients with metastatic sarcoma who progress on vascular endothelial growth factor receptor inhibitors (VEGFRi) have limited treatment options. Upregulation of the mTOR pathway has been demonstrated to be a means of resistance to targeted VEGFRi in metastatic sarcoma.Patients and methodsRetrospective cohort study to evaluate the clinical benefit at four months of combining mTOR inhibition (mTORi) via everolimus with VEGFRi in patients who have derived benefit from single-agent VEGFRi but have progressed. Patients with recurrent, metastatic soft tissue or bone sarcomas who progressed after deriving clinical benefit to VEGFRi beyond 12 weeks were continued on VEGFRi with the addition of everolimus (5 mg daily). Progression free survival was measured from start of VEGFRi to disease progression on single agent VEGFRi as well as from the addition of everolimus therapy to disease progression or drug discontinuation due to toxicity. Clinical benefit was defined as stable disease or partial response at 4 months.ResultsNine patients were evaluated. Two patients did not tolerate therapy due to GI toxicity and one elected to discontinue therapy. Of the remaining six patients, the clinical benefit rate at four months was 50%. Progression free survival (PFS) for these patients was 3.1 months ranging from 0.5 to 7.2 months with one patient remaining on combination therapy.ConclusionIn this heavily pre-treated, advanced sarcoma population, the addition of mTOR inhibition to VEGFRi based therapy resulted in a clinical benefit for a subset of patients. Prospective studies will be needed to verify these results.
Highlights
Soft tissue and bone sarcomas account for less than 1% of all adult cancers [1]
Metastatic soft tissue or bone sarcomas who progressed after deriving clinical benefit to vascular endothelial growth factor receptor inhibitors (VEGFRi) beyond 12 weeks were continued on VEGFRi with the addition of everolimus (5 mg daily)
In this heavily pre-treated, advanced sarcoma population, the addition of mammalian target of rapamycin (mTOR) inhibition to VEGFRi based therapy resulted in a clinical benefit for a subset of patients
Summary
Soft tissue and bone sarcomas account for less than 1% of all adult cancers [1]. While advancements in therapy have been made, median survival after development of distant metastases is 11 to 15 months [2]. Against VEGFR, have become a useful addition to our therapeutic armament as demonstrated by the vascular endothelial growth factor receptor inhibitor (VEGFRi) pazopanib receiving FDA approval [6], and new, promising, phase III data for regorafenib in the REGOSARC trial [7]. Other VEGFRi’s, including sorafenib and sunitinib have demonstrated activity in soft tissue or bone sarcomas with progression free survival on the order of 4 months [8,9]; similar to that seen in both the REGOSARC and PALLETTE trials [6,7]. Patients with metastatic sarcoma who progress on vascular endothelial growth factor receptor inhibitors (VEGFRi) have limited treatment options.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
