Background Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. Patients and Methods Clinical, prognostic, and treatment parameters in metastatic renal cell carcinoma patients with and without sarcomatoid histology treated with targeted therapy were retrospectively analyzed. Results Two thousand two hundred eighty-six patients were identified (sRCC: n = 230 and non-sRCC: n = 2056). sRCC patients had significantly worse IMDC prognostic criteria compared with non-sRCC (11% vs. 19% favorable risk; 49% vs. 57% intermediate risk, and 40% vs. 24% poor risk; P <.0001). Time from original diagnosis to relapse (excluding synchronous metastatic disease) was shorter in the sRCC group (18.8 vs. 42.9 months; P <.0001). There was no significant difference in the incidence of central nervous system metastases (6%-8%) or underlying clear cell histology (87%-88%). More than 93% of patients received VEGF inhibitors as first-line therapy; objective response was less common in sRCC whereas primary refractory disease was more common (21% vs. 26% and 43% vs. 21%; P <.0001, for both). sRCC patients had significantly less use of second- (P =.018) and third-line (P <.0001) systemic therapy. The median progression-free survival (PFS)/overall survival (OS) was 4.5/10.4 months in sRCC patients and 7.8/22.5 months in non-sRCC patients (P <.0001 for both). Sarcomatoid histology was associated with a significantly worse PFS and OS after adjusting for individual IMDC risk factors in multivariable analysis (hazard ratio, 1.5; P <.0001 for both). Conclusion Patients with sRCC have a shorter time to relapse, worse baseline prognostic criteria, and worse clinical outcome with targeted therapy. Additional insight into the biology of sRCC is needed to develop alternative therapeutics.
Bibliographical noteFunding Information:
Toni K. Choueiri has received research funding from Pfizer and has an advisory role at Aveo, Bayer, Genentech, GlaxoSmithKline, Novartis, and Pfizer. Jae-Lyun Lee has received honoraria from Bayer, Novartis, and Pfizer, and has received research funding from Bayer. Jennifer J. Knox has been a consultant and has played an advisory role at Aveo and has received research funding from Pfizer. Georg A. Bjarnason has been a consultant and has played an advisory role at Pfizer and has received honoraria and research funding from Pfizer. Lori A. Wood has been a consultant and has played an advisory role at Pfizer and has received research funding from Pfizer, Novartis, and GlaxoSmithKline. Frede Donskov has received research funding from Novartis and GlaxoSmithKline. Daniel Y. Heng is a consultant and has an advisory role at Bayer/Onyx, Novartis, and Pfizer. Brian I. Rini has an advisory role at Pfizer and has received research funding from Pfizer. The remaining authors have stated that they have no conflicts of interest.
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