Addition of Everolimus Post VEGFR Inhibition Treatment Failure in Advanced Sarcoma Patients Who Previously Benefited from VEGFR Inhibition: A Case Series.
BACKGROUND
Patients 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.


METHODS
Retrospective 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.


RESULTS
Nine 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.


CONCLUSIONS
In 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.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio, United States of America.
Adam C
http://orcid.org/0000-0003-3409-583X
AC
ElNaggar
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio, United States of America.|Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America.
John L
JL
Hays
Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America.|Division of Bioinformatics, Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio, United States of America.
James L
JL
Chen
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D000068338:Everolimus / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017211:Treatment Failure
D047428:Protein Kinase Inhibitors; D000068338:Everolimus; D040262:Receptors, Vascular Endothelial Growth Factor