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Discontinuing VEGF-targeted Therapy for Progression Versus Toxicity Affects Outcomes of Second-line Therapies in Metastatic Renal Cell Carcinoma

 Guillermo De Velasco  ;  Wanling Xie  ;  Frede Donskov  ;  Laurence Albiges  ;  Benoit Beuselinck  ;  Sandy Srinivas  ;  Neeraj Agarwal  ;  Jae Lyun Lee  ;  James Brugarolas  ;  Lori A. Wood  ;  Sun-young Rha  ;  Christian Kollmannsberger  ;  Scott North  ;  Ravindran Kanesvaran  ;  Brian I. Rini  ;  Reuben Broom  ;  Haru Yamamoto  ;  Marina D. Kaymakcalan  ;  Daniel Y.C. Heng  ;  Toni K. Choueiri 
 CLINICAL GENITOURINARY CANCER, Vol.15(3) : 403-410, 2017 
Journal Title
Issue Date
Antineoplastic Agents/adverse effects* ; Antineoplastic Agents/therapeutic use ; Carcinoma, Renal Cell/drug therapy* ; Disease Progression ; Female ; Humans ; Kidney Neoplasms/drug therapy* ; Male ; Molecular Targeted Therapy ; Neoplasm Metastasis ; Retrospective Studies ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists & inhibitors*
Discontinuation therapy ; Early discontinuation ; IMDC ; Systemic treatment ; VEGF-TT-intolerant patients
BACKGROUND: A significant subgroup of metastatic renal cell carcinoma (mRCC) patients discontinue vascular endothelial growth factor-targeted therapies (VEGF-TT) because of toxicity. Whether clinical outcomes differ in patients who receive second-line (2L) targeted therapy on the basis of reason for discontinuation of first-line (1L) therapy is unknown.

PATIENTS AND METHODS: Patients from 15 International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) centers who started 2L targeted therapy were included and the reason for discontinuation of 1L therapy retrospectively collected. Treatment outcomes of 2L, including response, time to treatment failure, and overall survival (OS) were assessed.

RESULTS: In total, 1124 patients were identified: 866 patients (77%) discontinued 1L VEGF-TT because of disease progression, and 208 patients (19%) because of toxicity. The reason for discontinuation of 1L therapy did not differ according to IMDC risk group. Compared with patients who stopped 1L VEGF-TT because of disease progression, patients who stopped because of toxicity had greater clinical benefit (nonprogressive disease as best response) in 2L treatment (68% vs. 56%; adjusted odds ratio, 1.58; 95% confidence interval [CI], 1.07-2.35; P = .023) and longer OS (17.4 vs. 11.2 months; adjusted hazard ratio, 0.69; 95% CI, 0.56-0.84; P = .0002) adjusted for type of therapy, time to initiation of 2L treatment, IMDC risk group, and number of metastases at initiation of 2L treatment.

CONCLUSION: mRCC patients who discontinue 1L VEGF-TT because of toxicity have better outcomes with 2L therapy than patients who stop therapy because of disease progression. These findings should be taken into consideration when designing clinical trials for 2L therapies in mRCC.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
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