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"
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MSK Authors
  1. Rana Kaplan
    7 Kaplan
  2. Dean Bajorin
    660 Bajorin
  3. David Solit
    780 Solit
  4. Scott R Gerst
    48 Gerst
  5. Gopakumar Vasudeva Iyer
    348 Iyer
  6. Lan Lin Gellert
    13 Gellert
  7. Arjun Vasant Balar
    12 Balar
  8. Alisa Trout
    14 Trout
  9. Ashley Regazzi
    92 Regazzi
  10. Deepa Pendse
    6 Pendse