@article{3122375,
    title = "The combination of bevacizumab/temsirolimus after first-line anti-VEGF therapy in advanced renal-cell carcinoma: a clinical and biomarker study",
    author = "Bamias, A. and Karavasilis, V. and Gavalas, N. and Tzannis, K. and Samantas, E. and Aravantinos, G. and Koutras, A. and Gkerzelis, I. and Kostouros, E. and Koutsoukos, K. and Zagouri, F. and Fountzilas, G. and Dimopoulos, M.-A.",
    journal = "International Journal of Clinical Oncology",
    year = "2019",
    volume = "24",
    number = "4",
    pages = "411-419",
    publisher = "Springer Tokyo",
    issn = "1341-9625, 1437-7772",
    doi = "10.1007/s10147-018-1361-9",
    keywords = "bevacizumab;  everolimus;  fibroblast growth factor;  fibroblast growth factor 2;  interferon;  pazopanib;  platelet derived growth factor alpha receptor;  platelet derived growth factor beta receptor;  platelet derived growth factor receptor;  sorafenib;  sunitinib;  temsirolimus;  vasculotropin;  vasculotropin A;  vasculotropin receptor 2;  antineoplastic agent;  bevacizumab;  MTOR protein, human;  pazopanib;  pyrimidine derivative;  rapamycin;  sorafenib;  sulfonamide;  sunitinib;  target of rapamycin kinase;  temsirolimus;  tumor marker;  vasculotropin A;  VEGFA protein, human, adult;  advanced cancer;  aged;  anemia;  Article;  cancer growth;  cancer prognosis;  cancer survival;  cancer therapy;  chest infection;  clinical article;  digestive system perforation;  disease association;  disease exacerbation;  drug dose reduction;  drug efficacy;  drug safety;  drug withdrawal;  epistaxis;  fatigue;  female;  follow up;  gastrointestinal disease;  human;  hypercholesterolemia;  hyperglycemia;  hypertension;  hypertriglyceridemia;  hyponatremia;  ileus;  infection;  intestine perforation;  kidney disease;  liver toxicity;  lung embolism;  male;  metabolic disorder;  mucosa inflammation;  nephrotoxicity;  neurologic disease;  neutropenia;  outcome assessment;  overall survival;  phase 2 clinical trial;  pneumonia;  priority journal;  progression free survival;  prospective study;  proteinuria;  relapse;  renal cell carcinoma;  skin disease;  skin toxicity;  thrombocytopenia;  time to treatment;  tooth disease;  treatment duration;  treatment failure;  treatment response;  analogs and derivatives;  antagonists and inhibitors;  blood;  clinical trial;  kidney tumor;  middle aged;  mortality;  pathology;  renal cell carcinoma;  tumor recurrence;  very elderly, Adult;  Aged;  Aged, 80 and over;  Antineoplastic Combined Chemotherapy Protocols;  Bevacizumab;  Biomarkers, Tumor;  Carcinoma, Renal Cell;  Humans;  Kidney Neoplasms;  Middle Aged;  Neoplasm Recurrence, Local;  Prospective Studies;  Pyrimidines;  Sirolimus;  Sorafenib;  Sulfonamides;  Sunitinib;  TOR Serine-Threonine Kinases;  Vascular Endothelial Growth Factor A",
    abstract = "Background: Vascular endothelial growth factor (VEGF) targeting represents the standard first-line therapy for metastatic renal-cell carcinoma (mRCC), while blocking the mammalian target of rapamycin (mTOR) is effective in relapsed disease. Since continuing blockade of VEGF may be of value, we studied the combination of bevacizumab with temsirolimus in mRCC patients relapsing after first-line treatment. Methods: A prospective, phase II study of the combination of bevacizumab (10 mg/kg, every 2 weeks) with temsirolimus (25 mg weekly) in patients with mRCC who failed first-line anti-VEGF treatment. 6-month progression-free survival (PFS) rate was the primary end point. The association of VEGFa, VEGFR2, fibroblast growth factor (FGF) b, platelet-derived growth factor receptor (PDGFR) a and PDGFRb with prognostic factors and outcomes were also studied. Results: 39 patients were enrolled. First-line therapy included: sunitinib (n = 16), bevacizumab/interferon (n = 12), pazopanib (n = 10), sorafenib (n = 1). After a median follow-up of 37 months, 6-month PFS rate was 50.9% [95% confidence interval (CI) 33.8–65.7], median time to progression 6.8 months (95% CI 5.5–9.2) and median overall survival (OS) 18.2 months (95% CI 12.9–27.2). Objective response rate was 27%. The most common AEs were metabolic (33%), renal (8%) and gastrointestinal (GI) (7%). The most common grade 3–5 AEs were GI (18%), infections (14%) and metabolic (25%). Toxicity was the most frequent cause of treatment discontinuation (40%). FGFb levels were associated with OS. Conclusions: In concert with recent data, our study confirms the efficacy of anti-VEGF/anti-mTOR combination in mRCC relapsing after anti-VEGF therapy. Toxicity was considerable leading to high rate of treatment discontinuations. Trial registration: ClinicalTrials.gov: NCT01264341. © 2018, Japan Society of Clinical Oncology."
}