Targeted Oncology

, Volume 8, Issue 3, pp 203–209

The association of clinical outcome to first-line VEGF-targeted therapy with clinical outcome to second-line VEGF-targeted therapy in metastatic renal cell carcinoma patients

  • Mhd Y. Al-Marrawi
  • Brian I. Rini
  • Lauren C. Harshman
  • Georg Bjarnason
  • Lori Wood
  • Ulka Vaishampayan
  • Mary MacKenzie
  • Jennifer J. Knox
  • Neeraj Agarwal
  • Hulayel Al-Harbi
  • Christian Kollmannsberger
  • Min-Han Tan
  • Sun Young Rha
  • Frede N. Donskov
  • Scott North
  • Toni K. Choueiri
  • Daniel Y. Heng
  • For the International mRCC Database Consortium
Original Research

DOI: 10.1007/s11523-012-0252-7

Cite this article as:
Al-Marrawi, M.Y., Rini, B.I., Harshman, L.C. et al. Targ Oncol (2013) 8: 203. doi:10.1007/s11523-012-0252-7

Abstract

There are many active drugs to treat metastatic renal cell carcinoma (mRCC) patients who progress through their first-line vascular endothelial growth factor (VEGF) inhibitor. Many clinicians choose a second-line VEGF inhibitor based on the type of response to first-line VEGF inhibitor, without data supporting this practice. This study was conducted to determine the association of response to second-line VEGF inhibitor with response to first-line VEGF inhibitor. All mRCC patients in participating centers of the International mRCC Database Consortium who were treated from January 2004 through June 2011 with a second-line VEGF inhibitor after failure of a different first-line VEGF inhibitor were retrospectively identified. The primary outcome is objective response rate (ORR) and the secondary outcome is progression-free survival (PFS) in each line of therapy. Of 1,602 total database patients, 464 patients received a first- and second-line VEGF inhibitor. The ORR to first-line therapy was 22 %, and the ORR to second-line therapy was 11 %. The ORR to second-line therapy was not different among patients achieving partial response versus stable disease versus progressive disease to first-line therapy (14 % vs. 10 % vs. 11 %, respectively; chi-squared trend test p = 0.17). The median PFS on first-line VEGF-targeted therapy was 7.5 months (95 % CI, 6.6–8.1), and the median PFS on second-line VEGF inhibitor was 3.9 months (95 % CI, 3.6–4.5). There was no correlation between first-line and second-line PFS (Pearson correlation coefficient 0.025; p = 0.59). The clinical response to a second-line VEGF inhibitor is not dependent on response to the first-line VEGF-inhibitor. Further studies are needed to define clinical parameters that predict response to second-line therapy to optimize the sequence of VEGF-targeted therapy in metastatic RCC patients.

Keywords

Association of TKIsFirst-line and second-line VEGF inhibitorsRenal cell cancerTyrosine kinase inhibitorsVEGF-targeted therapy

Copyright information

© Springer-Verlag France 2013

Authors and Affiliations

  • Mhd Y. Al-Marrawi
    • 1
  • Brian I. Rini
    • 1
  • Lauren C. Harshman
    • 3
  • Georg Bjarnason
    • 4
  • Lori Wood
    • 5
  • Ulka Vaishampayan
    • 6
  • Mary MacKenzie
    • 7
  • Jennifer J. Knox
    • 8
  • Neeraj Agarwal
    • 9
  • Hulayel Al-Harbi
    • 10
  • Christian Kollmannsberger
    • 11
  • Min-Han Tan
    • 12
  • Sun Young Rha
    • 14
  • Frede N. Donskov
    • 15
  • Scott North
    • 16
  • Toni K. Choueiri
    • 3
  • Daniel Y. Heng
    • 17
  • For the International mRCC Database Consortium
  1. 1.Taussig Cancer InstituteCleveland Clinic FoundationClevelandUSA
  2. 2.Cancer InstitutePenn State University/Hershey Medical CenterHersheyUSA
  3. 3.Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute/Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  4. 4.Sunnybrook Odette Cancer CentreTorontoCanada
  5. 5.Queen Elizabeth II Health Sciences CenterHalifaxCanada
  6. 6.Karmanos Cancer InstituteWayne State UniversityDetroitUSA
  7. 7.London Health Sciences CenterLondonCanada
  8. 8.Princess Margaret HospitalUniversity of TorontoTorontoCanada
  9. 9.Division of Medical Oncology, Huntsman Cancer InstituteUniversity of UtahSalt Lake CityUSA
  10. 10.University of CalgaryCalgaryCanada
  11. 11.Vancouver Cancer CenterBritish Columbia Cancer AgencyVancouverCanada
  12. 12.Institute of Bioengineering and NanotechnologyNational Cancer Centre SingaporeSingaporeSingapore
  13. 13.Institute of Bioengineering and NanotechnologySingaporeSingapore
  14. 14.Yonsei Cancer CenterYonsei University College of MedicineSeoulSouth Korea
  15. 15.Department of OncologyAarhus University HospitalAarhusDenmark
  16. 16.Cross Cancer InstituteUniversity of AlbertaEdmontonCanada
  17. 17.Tom Baker Cancer CentreUniversity of CalgaryCalgaryCanada