A phase 2 trial of sunitinib in patients with advanced non-clear cell renal cell carcinoma

Nizar M. Tannir, Elizabeth Plimack, Chaan Ng, Pheroze Tamboli, Nebiyou B. Bekele, Lianchun Xiao, Lisa Smith, Zita Lim, Lance Pagliaro, John Araujo, Ana Aparicio, Surena Matin, Christopher G. Wood, Eric Jonasch

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Background: Sunitinib is a standard-of-care treatment in advanced clear cell renal cell carcinoma (ccRCC). Retrospective and expanded access data suggest sunitinib has activity in advanced non-clear cell renal cell carcinoma (nccRCC). Objective: To prospectively determine the clinical efficacy and safety of sunitinib in patients with advanced nccRCC. Design, setting, and participants: This is a single-arm phase 2 trial with a two-stage design. Eligibility criteria included pathologically confirmed nccRCC or ccRCC with ≥20% sarcomatoid histology, performance status 0-2, measurable disease, a maximum of two prior systemic therapies, and no prior treatment with tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptors. Intervention: Patients received sunitinib 50 mg daily on a 4-wk on, 2-wk off schedule. Outcome measurements and statistical analysis: Primary end points were objective response rate (ORR) and progression-free survival (PFS). Secondary end points were safety and overall survival (OS). Results and limitations: Fifty-seven patients were eligible (nccRCC histology: papillary, 27; chromophobe, 5; unclassified, 8; collecting duct or medullary carcinoma, 6; sarcomatoid, 7; and others, 4). Median PFS for 55 evaluable patients was 2.7 mo (95% confidence interval [CI], 1.4-5.4). Two patients with chromophobe and one patient with unclassified histology had a confirmed partial response (5% ORR). Median PFS for patients with papillary histology was 1.6 mo (95% CI, 1.4-5.4). Median PFS for patients with chromophobe histology was 12.7 mo (95% CI, 8.5-NA). Median OS for all patients was 16.8 mo (95% CI, 10.7-26.3). Treatment-emergent adverse events were consistent with sunitinib's mechanism of action. The nonrandomized design and small number of patients are limitations of this study. Conclusions: The differential response of chromophobe histology to sunitinib suggests a therapeutically relevant biological heterogeneity exists within nccRCC. The low ORR and short PFS with sunitinib in the other nccRCC subtypes underscore the need to enroll patients with these diverse tumors in clinical trials.

Original languageEnglish (US)
Pages (from-to)1013-1019
Number of pages7
JournalEuropean Urology
Volume62
Issue number6
DOIs
StatePublished - Dec 2012
Externally publishedYes

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Renal Cell Carcinoma
Histology
Disease-Free Survival
Confidence Intervals
sunitinib
Safety
Medullary Carcinoma
Vascular Endothelial Growth Factor Receptor
Survival
Therapeutics
Standard of Care
Protein-Tyrosine Kinases
Appointments and Schedules
Clinical Trials

Keywords

  • Chromophobe renal cell carcinoma
  • Non-clear cell renal cell carcinoma
  • Papillary renal cell carcinoma
  • Renal cell carcinoma variant histology
  • Sunitinib
  • Targeted therapy

ASJC Scopus subject areas

  • Urology

Cite this

Tannir, N. M., Plimack, E., Ng, C., Tamboli, P., Bekele, N. B., Xiao, L., ... Jonasch, E. (2012). A phase 2 trial of sunitinib in patients with advanced non-clear cell renal cell carcinoma. European Urology, 62(6), 1013-1019. https://doi.org/10.1016/j.eururo.2012.06.043

A phase 2 trial of sunitinib in patients with advanced non-clear cell renal cell carcinoma. / Tannir, Nizar M.; Plimack, Elizabeth; Ng, Chaan; Tamboli, Pheroze; Bekele, Nebiyou B.; Xiao, Lianchun; Smith, Lisa; Lim, Zita; Pagliaro, Lance; Araujo, John; Aparicio, Ana; Matin, Surena; Wood, Christopher G.; Jonasch, Eric.

In: European Urology, Vol. 62, No. 6, 12.2012, p. 1013-1019.

Research output: Contribution to journalArticle

Tannir, NM, Plimack, E, Ng, C, Tamboli, P, Bekele, NB, Xiao, L, Smith, L, Lim, Z, Pagliaro, L, Araujo, J, Aparicio, A, Matin, S, Wood, CG & Jonasch, E 2012, 'A phase 2 trial of sunitinib in patients with advanced non-clear cell renal cell carcinoma', European Urology, vol. 62, no. 6, pp. 1013-1019. https://doi.org/10.1016/j.eururo.2012.06.043
Tannir, Nizar M. ; Plimack, Elizabeth ; Ng, Chaan ; Tamboli, Pheroze ; Bekele, Nebiyou B. ; Xiao, Lianchun ; Smith, Lisa ; Lim, Zita ; Pagliaro, Lance ; Araujo, John ; Aparicio, Ana ; Matin, Surena ; Wood, Christopher G. ; Jonasch, Eric. / A phase 2 trial of sunitinib in patients with advanced non-clear cell renal cell carcinoma. In: European Urology. 2012 ; Vol. 62, No. 6. pp. 1013-1019.
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abstract = "Background: Sunitinib is a standard-of-care treatment in advanced clear cell renal cell carcinoma (ccRCC). Retrospective and expanded access data suggest sunitinib has activity in advanced non-clear cell renal cell carcinoma (nccRCC). Objective: To prospectively determine the clinical efficacy and safety of sunitinib in patients with advanced nccRCC. Design, setting, and participants: This is a single-arm phase 2 trial with a two-stage design. Eligibility criteria included pathologically confirmed nccRCC or ccRCC with ≥20{\%} sarcomatoid histology, performance status 0-2, measurable disease, a maximum of two prior systemic therapies, and no prior treatment with tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptors. Intervention: Patients received sunitinib 50 mg daily on a 4-wk on, 2-wk off schedule. Outcome measurements and statistical analysis: Primary end points were objective response rate (ORR) and progression-free survival (PFS). Secondary end points were safety and overall survival (OS). Results and limitations: Fifty-seven patients were eligible (nccRCC histology: papillary, 27; chromophobe, 5; unclassified, 8; collecting duct or medullary carcinoma, 6; sarcomatoid, 7; and others, 4). Median PFS for 55 evaluable patients was 2.7 mo (95{\%} confidence interval [CI], 1.4-5.4). Two patients with chromophobe and one patient with unclassified histology had a confirmed partial response (5{\%} ORR). Median PFS for patients with papillary histology was 1.6 mo (95{\%} CI, 1.4-5.4). Median PFS for patients with chromophobe histology was 12.7 mo (95{\%} CI, 8.5-NA). Median OS for all patients was 16.8 mo (95{\%} CI, 10.7-26.3). Treatment-emergent adverse events were consistent with sunitinib's mechanism of action. The nonrandomized design and small number of patients are limitations of this study. Conclusions: The differential response of chromophobe histology to sunitinib suggests a therapeutically relevant biological heterogeneity exists within nccRCC. The low ORR and short PFS with sunitinib in the other nccRCC subtypes underscore the need to enroll patients with these diverse tumors in clinical trials.",
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T1 - A phase 2 trial of sunitinib in patients with advanced non-clear cell renal cell carcinoma

AU - Tannir, Nizar M.

AU - Plimack, Elizabeth

AU - Ng, Chaan

AU - Tamboli, Pheroze

AU - Bekele, Nebiyou B.

AU - Xiao, Lianchun

AU - Smith, Lisa

AU - Lim, Zita

AU - Pagliaro, Lance

AU - Araujo, John

AU - Aparicio, Ana

AU - Matin, Surena

AU - Wood, Christopher G.

AU - Jonasch, Eric

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N2 - Background: Sunitinib is a standard-of-care treatment in advanced clear cell renal cell carcinoma (ccRCC). Retrospective and expanded access data suggest sunitinib has activity in advanced non-clear cell renal cell carcinoma (nccRCC). Objective: To prospectively determine the clinical efficacy and safety of sunitinib in patients with advanced nccRCC. Design, setting, and participants: This is a single-arm phase 2 trial with a two-stage design. Eligibility criteria included pathologically confirmed nccRCC or ccRCC with ≥20% sarcomatoid histology, performance status 0-2, measurable disease, a maximum of two prior systemic therapies, and no prior treatment with tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptors. Intervention: Patients received sunitinib 50 mg daily on a 4-wk on, 2-wk off schedule. Outcome measurements and statistical analysis: Primary end points were objective response rate (ORR) and progression-free survival (PFS). Secondary end points were safety and overall survival (OS). Results and limitations: Fifty-seven patients were eligible (nccRCC histology: papillary, 27; chromophobe, 5; unclassified, 8; collecting duct or medullary carcinoma, 6; sarcomatoid, 7; and others, 4). Median PFS for 55 evaluable patients was 2.7 mo (95% confidence interval [CI], 1.4-5.4). Two patients with chromophobe and one patient with unclassified histology had a confirmed partial response (5% ORR). Median PFS for patients with papillary histology was 1.6 mo (95% CI, 1.4-5.4). Median PFS for patients with chromophobe histology was 12.7 mo (95% CI, 8.5-NA). Median OS for all patients was 16.8 mo (95% CI, 10.7-26.3). Treatment-emergent adverse events were consistent with sunitinib's mechanism of action. The nonrandomized design and small number of patients are limitations of this study. Conclusions: The differential response of chromophobe histology to sunitinib suggests a therapeutically relevant biological heterogeneity exists within nccRCC. The low ORR and short PFS with sunitinib in the other nccRCC subtypes underscore the need to enroll patients with these diverse tumors in clinical trials.

AB - Background: Sunitinib is a standard-of-care treatment in advanced clear cell renal cell carcinoma (ccRCC). Retrospective and expanded access data suggest sunitinib has activity in advanced non-clear cell renal cell carcinoma (nccRCC). Objective: To prospectively determine the clinical efficacy and safety of sunitinib in patients with advanced nccRCC. Design, setting, and participants: This is a single-arm phase 2 trial with a two-stage design. Eligibility criteria included pathologically confirmed nccRCC or ccRCC with ≥20% sarcomatoid histology, performance status 0-2, measurable disease, a maximum of two prior systemic therapies, and no prior treatment with tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptors. Intervention: Patients received sunitinib 50 mg daily on a 4-wk on, 2-wk off schedule. Outcome measurements and statistical analysis: Primary end points were objective response rate (ORR) and progression-free survival (PFS). Secondary end points were safety and overall survival (OS). Results and limitations: Fifty-seven patients were eligible (nccRCC histology: papillary, 27; chromophobe, 5; unclassified, 8; collecting duct or medullary carcinoma, 6; sarcomatoid, 7; and others, 4). Median PFS for 55 evaluable patients was 2.7 mo (95% confidence interval [CI], 1.4-5.4). Two patients with chromophobe and one patient with unclassified histology had a confirmed partial response (5% ORR). Median PFS for patients with papillary histology was 1.6 mo (95% CI, 1.4-5.4). Median PFS for patients with chromophobe histology was 12.7 mo (95% CI, 8.5-NA). Median OS for all patients was 16.8 mo (95% CI, 10.7-26.3). Treatment-emergent adverse events were consistent with sunitinib's mechanism of action. The nonrandomized design and small number of patients are limitations of this study. Conclusions: The differential response of chromophobe histology to sunitinib suggests a therapeutically relevant biological heterogeneity exists within nccRCC. The low ORR and short PFS with sunitinib in the other nccRCC subtypes underscore the need to enroll patients with these diverse tumors in clinical trials.

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KW - Renal cell carcinoma variant histology

KW - Sunitinib

KW - Targeted therapy

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