title: 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.
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.
authors.affiliation: Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Mhd Y
authors.initials: MY
authors.lastname: Al-Marrawi
authors.affiliation: Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.affiliation: Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Harshman
authors.affiliation: Sunnybrook Odette Cancer Centre, Toronto, ON, Canada.
authors.forename: Georg
authors.initials: G
authors.lastname: Bjarnason
authors.affiliation: Queen Elizabeth II Health Sciences Center, Halifax, NS, Canada.
authors.forename: Lori
authors.initials: L
authors.lastname: Wood
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
authors.forename: Ulka
authors.initials: U
authors.lastname: Vaishampayan
authors.affiliation: London Health Sciences Center, London, ON, Canada.
authors.forename: Mary
authors.initials: M
authors.lastname: MacKenzie
authors.affiliation: Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.affiliation: Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Agarwal
authors.affiliation: University of Calgary, Calgary, AB, Canada.
authors.forename: Hulayel
authors.initials: H
authors.lastname: Al-Harbi
authors.affiliation: Vancouver Cancer Center, British Columbia Cancer Agency, Vancouver, BC, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Kollmannsberger
authors.affiliation: Institute of Bioengineering and Nanotechnology, National Cancer Centre Singapore, Singapore, Singapore.
authors.forename: Min-Han
authors.initials: MH
authors.lastname: Tan
authors.affiliation: Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.affiliation: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Frede N
authors.initials: FN
authors.lastname: Donskov
authors.affiliation: Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: North
authors.affiliation: Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Tom Baker Cancer Centre, University of Calgary, 1331 29th St NW, Calgary, AB, T2N 4N2, Canada. daniel.heng@albertahealthservices.ca.
authors.forename: Daniel Y
authors.initials: DY
authors.lastname: Heng
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D012189:Retrospective Studies; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases