title: Randomized Open-Label Phase II Trial of Apitolisib (GDC-0980), a Novel Inhibitor of the PI3K/Mammalian Target of Rapamycin Pathway, Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma.
abstract: To the best of our knowledge, this study is the first to compare dual inhibition of PI3K/mammalian target of rapamycin (mTOR) by apitolisib (GDC-0980) against single inhibition of mTORC1 by everolimus in metastatic renal cell carcinoma (mRCC).
  
  
  
  Patients with clear-cell mRCC who progressed on or after vascular endothelial growth factor-targeted therapy were randomly assigned to apitolisib 40 mg once per day or to everolimus 10 mg once per day. End points included progression-free survival, safety, overall survival, and objective response rate. Biomarker assessments were conducted.
  
  
  
  Eighty-five patients were randomly assigned. After 67 events, stratified analysis revealed that median progression-free survival was significantly shorter for apitolisib than for everolimus (3.7 v 6.1 months; hazard ratio, 2.12 [95% CI, 1.23 to 3.63; P < .01]); apitolisib was not favored in any stratification subgroup. Median overall survival was not significantly different but trended in favor of everolimus (16.5 v 22.8 months; hazard ratio, 1.77 [95% CI, 0.97 to 3.24; P = .06]). The objective response rate was 7.1% for apitolisib and 11.6% for everolimus. Patients administered apitolisib with a greater incidence of grade 3 to 4 adverse events were more likely to discontinue treatment (31% v 12% for everolimus). No drug-related deaths were observed. Apitolisib in comparison with everolimus was associated with substantially more high-grade hyperglycemia (40% v 9%) and rash (24% v 2%). Apitolisib pharmacokinetics suggested a relationship between exposure, and rash and hyperglycemia. Retrospective biomarker analyses revealed a relationship between VHL mutation status and outcome with everolimus but not with apitolisib. High hypoxia-inducible factor 1α protein expression was associated with better outcome in both arms.
  
  
  
  This study demonstrated that dual PI3K/mTOR inhibition by apitolisib was less effective than was everolimus in mRCC, likely because full blockade of PI3K/mTOR signaling resulted in multiple on-target adverse events. VHL mutation and hypoxia-inducible factor 1α expression may be predictive of an mTOR inhibitor benefit, although prospective validation is required.
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany thomas.powles@bartsandthelondon.nhs.uk.
authors.forename: Thomas
authors.initials: T
authors.lastname: Powles
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Lackner
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Oudard
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Christy
authors.initials: C
authors.lastname: Ralph
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Brown
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hawkins
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Castellano
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Staehler
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Alain
authors.initials: A
authors.lastname: Ravaud
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Bridget
authors.initials: B
authors.lastname: O'Keeffe
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Yulei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Spoerke
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Ling-Yuh
authors.initials: LY
authors.lastname: Huw
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Michelle
authors.initials: M
authors.lastname: Byrtek
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Ware
authors.affiliation: Thomas Powles, Queen Mary University of London, London; Christy Ralph, University of Leeds, Leeds; Janet E. Brown, University of Sheffield, Sheffield; Robert E. Hawkins, University of Manchester, Manchester, United Kingdom; Mark R. Lackner, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling Yuh Huw, Michelle Byrtek, Rui Zhu, and Joseph A. Ware, Genentech, South San Francisco, CA; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Bernard Escudier, Institut Gustave Roussy, Villejuif; Alain Ravaud, Hospital Saint Andre, Bordeaux; Stéphane Oudard, University Paris Descartes, Paris, France; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; and Michael D. Staehler, University Hospital Munich-Grosshadern, Marchioninistrasse, Germany.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D018572:Disease-Free Survival; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: C569670:1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno(3,2-d)pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D019086:Bridged Bicyclo Compounds, Heterocyclic; D046912:Multiprotein Complexes; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011743:Pyrimidines; D000068338:Everolimus; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases