TY - JOUR
T1 - Metastatic Chromophobe Renal Cell Carcinoma
T2 - Presence or Absence of Sarcomatoid Differentiation Determines Clinical Course and Treatment Outcomes
AU - Ged, Yasser
AU - Chen, Ying Bei
AU - Knezevic, Andrea
AU - Casuscelli, Jozefina
AU - Redzematovic, Almedina
AU - DiNatale, Renzo G.
AU - Carlo, Maria I.
AU - Lee, Chung Han
AU - Feldman, Darren R.
AU - Patil, Sujata
AU - Hakimi, A. Ari
AU - Russo, Paul
AU - Motzer, Robert J.
AU - Voss, Martin H.
N1 - Funding Information:
Funding for this work by the Precision Immunotherapy Kidney Cancer Program, Tuttle Rare Kidney Cancer Fund, Center Core Grant P30 CA008748 from the National Cancer Institute .
Funding Information:
M.H.V. reports receiving commercial research grants from Bristol-Myers Squibb and Genentech/Roche; honoraria from Novartis; travel/accommodation from Eisai, Novartis, and Takeda; consultant/advisory board member for Alexion Pharmaceuticals, Bayer, Calithera Biosciences, Corvus Pharmaceuticals, Exelixis, Eisai, GlaxoSmithKline, Natera, Novartis, and Pfizer. R.J.M. reports receiving commercial research grants from Pfizer, Eisai, Exelixis, Bristol-Myers Squibb, Genentech/Roche, and Novartis, and is a consultant/advisory board member for Pfizer, Merck, Genentech, Exelixis, Eisai, and Novartis. C.-H.L. reports a consulting/advisory role for Exelexis and Eisai. M.I.C. reports a consulting/advisory role for Pfizer. D.R.F. reports research support from Novartis and Seattle Genetics. All other authors state that they have no conflicts of interest.Funding for this work by the Precision Immunotherapy Kidney Cancer Program, Tuttle Rare Kidney Cancer Fund, Center Core Grant P30 CA008748 from the National Cancer Institute.
Publisher Copyright:
© 2019
PY - 2019/6
Y1 - 2019/6
N2 - Background: Sarcomatoid features (SF) in renal cell carcinoma (RCC) denote poor prognosis. Data for metastatic chromophobe RCC (ChRCC) with SF are limited. We studied clinical outcomes and genomic features in this setting. Patients and Methods: We performed a retrospective review of newly diagnosed metastatic ChRCC patients; end points included overall survival (OS), time to treatment failure (TTF), and time to metastatic recurrence (TTR) after nephrectomy for localized disease. A subset of patients underwent next-generation sequencing (NGS). Outcomes were compared using nonparametric tests. Results: One hundred nine patients with metastatic ChRCC were identified including 29 with SF. Median TTR after nephrectomy was shorter for patients with versus without SF (2.7 months [95% confidence interval (CI), 0.7-6.9] versus 48.8 months [95% CI, 30.8-80.7], log rank P <.001). Median TTF during first-line therapy was shorter for patients with versus without SF (1.8 months [95% CI, 0.9-2.7] vs. 8.0 months [95% CI, 5.1-13.0]; log rank P <.001). No responses were observed in 6 patients treated with nivolumab including 4 with SF. Median OS was inferior for patients with versus without SF (38 months vs.7.5 months; hazard ratio, 4.7 [95% CI, 2.7-8.2]; P <.001). NGS, performed in 22 patients, showed that 64% and 45% harbored tumor protein P53 and phosphatase and tensin homolog alterations, respectively. Microsatellite instability high status was identified in 3 patients. Conclusion: Metastatic ChRCC patients with SF had worse outcomes compared with those without SF. Median TTR < 3 months for this subgroup supports close surveillance after nephrectomy for localized tumors. Lack of benefit with various systemic regimens warrants studying underlying biology and investigating novel agents.
AB - Background: Sarcomatoid features (SF) in renal cell carcinoma (RCC) denote poor prognosis. Data for metastatic chromophobe RCC (ChRCC) with SF are limited. We studied clinical outcomes and genomic features in this setting. Patients and Methods: We performed a retrospective review of newly diagnosed metastatic ChRCC patients; end points included overall survival (OS), time to treatment failure (TTF), and time to metastatic recurrence (TTR) after nephrectomy for localized disease. A subset of patients underwent next-generation sequencing (NGS). Outcomes were compared using nonparametric tests. Results: One hundred nine patients with metastatic ChRCC were identified including 29 with SF. Median TTR after nephrectomy was shorter for patients with versus without SF (2.7 months [95% confidence interval (CI), 0.7-6.9] versus 48.8 months [95% CI, 30.8-80.7], log rank P <.001). Median TTF during first-line therapy was shorter for patients with versus without SF (1.8 months [95% CI, 0.9-2.7] vs. 8.0 months [95% CI, 5.1-13.0]; log rank P <.001). No responses were observed in 6 patients treated with nivolumab including 4 with SF. Median OS was inferior for patients with versus without SF (38 months vs.7.5 months; hazard ratio, 4.7 [95% CI, 2.7-8.2]; P <.001). NGS, performed in 22 patients, showed that 64% and 45% harbored tumor protein P53 and phosphatase and tensin homolog alterations, respectively. Microsatellite instability high status was identified in 3 patients. Conclusion: Metastatic ChRCC patients with SF had worse outcomes compared with those without SF. Median TTR < 3 months for this subgroup supports close surveillance after nephrectomy for localized tumors. Lack of benefit with various systemic regimens warrants studying underlying biology and investigating novel agents.
KW - Genomics
KW - Non–clear-cell renal cell carcinoma
KW - Retrospective analysis
KW - Survival
KW - Systemic therapy
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U2 - 10.1016/j.clgc.2019.03.018
DO - 10.1016/j.clgc.2019.03.018
M3 - Article
C2 - 31036466
AN - SCOPUS:85064712386
SN - 1558-7673
VL - 17
SP - e678-e688
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 3
ER -