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

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalClinical Genitourinary Cancer
DOIs
StateAccepted/In press - Nov 7 2016

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Renal Cell Carcinoma
Vascular Endothelial Growth Factor A
Therapeutics
Disease Progression
Confidence Intervals
Survival
Treatment Failure
Reaction Time

Keywords

  • Discontinuation therapy
  • Early discontinuation
  • IMDC
  • Systemic treatment
  • VEGF-TT-intolerant patients

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Discontinuing VEGF-targeted Therapy for Progression Versus Toxicity Affects Outcomes of Second-line Therapies in Metastatic Renal Cell Carcinoma. / De Velasco, Guillermo; Xie, Wanling; Donskov, Frede; Albiges, Laurence; Beuselinck, Benoit; Srinivas, Sandy; Agarwal, Neeraj; Lee, Jae Lyun; Brugarolas, James; Wood, Lori A.; Rha, Sun young; Kollmannsberger, Christian; North, Scott; Kanesvaran, Ravindran; Rini, Brian I.; Broom, Reuben; Yamamoto, Haru; Kaymakcalan, Marina D.; Heng, Daniel Y C; Choueiri, Toni K.

In: Clinical Genitourinary Cancer, 07.11.2016.

Research output: Contribution to journalArticle

De Velasco, G, Xie, W, Donskov, F, Albiges, L, Beuselinck, B, Srinivas, S, Agarwal, N, Lee, JL, Brugarolas, J, Wood, LA, Rha, SY, Kollmannsberger, C, North, S, Kanesvaran, R, Rini, BI, Broom, R, Yamamoto, H, Kaymakcalan, MD, Heng, DYC & Choueiri, TK 2016, 'Discontinuing VEGF-targeted Therapy for Progression Versus Toxicity Affects Outcomes of Second-line Therapies in Metastatic Renal Cell Carcinoma', Clinical Genitourinary Cancer. https://doi.org/10.1016/j.clgc.2017.01.005
De Velasco, Guillermo ; Xie, Wanling ; Donskov, Frede ; Albiges, Laurence ; Beuselinck, Benoit ; Srinivas, Sandy ; Agarwal, Neeraj ; Lee, Jae Lyun ; Brugarolas, James ; Wood, Lori A. ; Rha, Sun young ; Kollmannsberger, Christian ; North, Scott ; Kanesvaran, Ravindran ; Rini, Brian I. ; Broom, Reuben ; Yamamoto, Haru ; Kaymakcalan, Marina D. ; Heng, Daniel Y C ; Choueiri, Toni K. / Discontinuing VEGF-targeted Therapy for Progression Versus Toxicity Affects Outcomes of Second-line Therapies in Metastatic Renal Cell Carcinoma. In: Clinical Genitourinary Cancer. 2016.
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abstract = "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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T1 - Discontinuing VEGF-targeted Therapy for Progression Versus Toxicity Affects Outcomes of Second-line Therapies in Metastatic Renal Cell Carcinoma

AU - De Velasco, Guillermo

AU - Xie, Wanling

AU - Donskov, Frede

AU - Albiges, Laurence

AU - Beuselinck, Benoit

AU - Srinivas, Sandy

AU - Agarwal, Neeraj

AU - Lee, Jae Lyun

AU - Brugarolas, James

AU - Wood, Lori A.

AU - Rha, Sun young

AU - Kollmannsberger, Christian

AU - North, Scott

AU - Kanesvaran, Ravindran

AU - Rini, Brian I.

AU - Broom, Reuben

AU - Yamamoto, Haru

AU - Kaymakcalan, Marina D.

AU - Heng, Daniel Y C

AU - Choueiri, Toni K.

PY - 2016/11/7

Y1 - 2016/11/7

N2 - 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.

AB - 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.

KW - Discontinuation therapy

KW - Early discontinuation

KW - IMDC

KW - Systemic treatment

KW - VEGF-TT-intolerant patients

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