Phase II study of everolimus in metastatic urothelial cancer Journal Article


Authors: Milowsky, M. I.; Iyer, G.; Regazzi, A. M.; Al-Ahmadie, H.; Gerst, S. R.; Ostrovnaya, I.; Gellert, L. L.; Kaplan, R.; Garcia-Grossman, I. R.; Pendse, D.; Balar, A. V.; Flaherty, A. M.; Trout, A.; Solit, D. B.; Bajorin, D. F.
Article Title: Phase II study of everolimus in metastatic urothelial cancer
Abstract: Objective To assess the efficacy and tolerability of everolimus in advanced urothelial carcimoma (UC). Patients and Methods The present study comprised a single-arm, non-randomized study in which all patients received everolimus 10 mg orally once daily continuously (one cycle = 4 weeks). In total, 45 patients with metastatic UC progressing after one to four cytotoxic agents were enrolled between February 2009 and November 2010 at the Memorial Sloan-Kettering Cancer Center. The primary endpoints were 2-month progression-free survival (PFS) and the safety of everolimus, with the secondary endpoint being the response rate. A Simon minimax two-stage design tested the null hypothesis that the true two month PFS rate was ≤50%, as opposed to the alternative hypothesis of ≥70%. Results The most common grade 3/4 toxicities were fatigue, infection, anaemia, lymphopaenia, hyperglycaemia and hypophosphataemia. There were two partial responses in nodal metastases, with one patient achieving a 94% decrease in target lesions and remaining on drug at 26 months. An additional 12 patients exhibited minor tumour regression. There were 23 of 45 (51%) patients who were progression-free at 2 months with a median (95% CI) PFS of 2.6 (1.8-3.5) months and a median (95% CI) overall survival of 8.3 (5.5-12.1) months. No clear association was observed between mammalian target of rapamycin pathway marker expression and 2-month PFS. Conclusions Although everolimus did not meet its primary endpoint, one partial response, one near-complete response and twelve minor regressions were observed. Everolimus possesses meaningful anti-tumour activity in a subset of patients with advanced UC. Studies aiming to define the genetic basis of everolimus activity in individual responders are ongoing. © 2013 BJU International.
Keywords: s6 kinase; adult; clinical article; human tissue; aged; aged, 80 and over; middle aged; gene mutation; overall survival; constipation; drug tolerability; fatigue; neutropenia; cytotoxic agent; advanced cancer; diarrhea; drug efficacy; drug withdrawal; hypophosphatemia; side effect; antineoplastic agents; lymph node metastasis; gene; edema; progression free survival; drug eruption; infection; multiple cycle treatment; pain; phase 2 clinical trial; anemia; bleeding; leukopenia; mucosa inflammation; nausea; neuropathy; thrombocytopenia; dehydration; weight reduction; kidney failure; tumor regression; bladder cancer; fibroblast growth factor receptor 3; oncogene h ras; urinary bladder neoplasms; coughing; drug fever; dyspnea; flushing; hyperglycemia; hypomagnesemia; lymphocytopenia; pneumonia; pruritus; hypoxia; chemotherapy induced emesis; confusion; hyperkalemia; hypoalbuminemia; hypokalemia; hyponatremia; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; urinary tract infection; muscle weakness; urinary frequency; xerostomia; initiation factor 4e binding protein 1; enteritis; visceral metastasis; hyperbilirubinemia; heartburn; urinary urgency; hypercholesterolemia; heart arrhythmia; gastroesophageal reflux; carcinoma, transitional cell; clinical trials, phase ii as topic; dry skin; transitional cell carcinoma; urothelial cancer; everolimus; b raf kinase; pik3ca gene; sirolimus; hypertriglyceridemia; mtor; bronchitis; hypernatremia; partial thromboplastin time; dysgeusia; braf gene; myositis; international normalized ratio; prosthesis infection; perianal abscess; fgfr3 gene
Journal Title: BJU International
Volume: 112
Issue: 4
ISSN: 1464-4096
Publisher: Wiley Blackwell  
Date Published: 2013-08-01
Start Page: 462
End Page: 470
Language: English
DOI: 10.1111/j.1464-410X.2012.11720.x
PROVIDER: scopus
PUBMED: 23551593
PMCID: PMC4020005
DOI/URL:
Notes: --- - "Export Date: 4 September 2013" - "CODEN: BJINF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Rana Kaplan
    4 Kaplan
  2. Dean Bajorin
    413 Bajorin
  3. David Solit
    435 Solit
  4. Scott R Gerst
    42 Gerst
  5. Gopakumar Vasudeva Iyer
    126 Iyer
  6. Lan Lin Gellert
    11 Gellert
  7. Arjun Vasant Balar
    9 Balar
  8. Alisa Trout
    13 Trout
  9. Ashley Regazzi
    35 Regazzi
  10. Deepa Pendse
    3 Pendse