Genitourinary Oncology Service, Division of Oncology, Meir Medical Center, Sackler School of Medicine, Tel Aviv University, Kfar-Saba, Israel
Daniel Keizman , David Sarid , Jae-Lyun Lee , Maya Gottfried , Natalie Maimon , Avishay Sella , Hans J. Hammers , Mario A. Eisenberger , Michael Anthony Carducci , Victoria J. Sinibaldi , Victoria Neiman , Eli Rosenbaum , Eli Gez , Avivit Peer , Wilmosh Mermershtain , Keren Rouvinov , Raanan Berger , Ibrahim Yildiz
Background: Sunitinib (Su) is a standard therapy (tx) for mccRCC. Data on its activity in the rare variant of metastatic chromophobe renal cell carcinoma (mchRCC) are limited by very small or heterogeneous (mixed histology with papillary type, or mixed targeted therapies) studies. We analyzed the activity of Su in a relatively large and homogenous international cohort of mchRCC pts, in terms of outcome and comparison to mccRCC. Methods: Records from mchRCC pts treated with first-line Su in 9 centers across 4 countries were retrospectively reviewed. Univariate and multivariate analyses of association between clinicopathologic factors and outcome were performed. Subsequently, mchRCC pts were individually matched to mccRCC pts. We compared the response rate (RR), progression free survival (PFS), and overall survival (OS) between the groups. Results: Between 2004-2014, 33 pts (median age 64, 45% male) with mchRCC were treated with Su as first-line tx. 76% had a prior nephrectomy. HENG risk was good 27%, intermediate 55%, and poor 18%. 33% were active smokers, and 30% users of angiotensin system inhibitors (ASIs). 55%, 27%, and 33% had lung, liver, and bone metastases, respectively. 48% had a pre-tx neutrophil to lymphocyte ratio (NLR) >3. 42% had dose reduction/tx interruption (DR/TI). Su-induced hypertension (HTN) occurred in 48%. 75% achieved a clinical benefit (partial response + stable disease), while 25% had disease progression within the first 3 months of tx. Median PFS and OS were 10 and 26 months, respectively. Factors associated with PFS were the HENG risk (HR 3.8, p=0.025) and pre-tx NLR >3 (HR 0.6, p=0.012). Factors associated with OS were the HENG risk (HR 4.27, p=0.027), liver metastases (HR 4.6, p=0.029), and pre-treatment NLR <3 (HR 0.5, p=0.04). Tx outcome was not significantly different between mchRCC pts and mccRCC pts, who were individually matched by HENG risk, nephrectomy/smoking status, pre-tx NLR, use of ASIs, DR/TI, and Su induced HTN. In mccRCC pts (p value versus mchRCC), 70% achieved a clinical benefit (p=0.58), and median PFS and OS were 9 (p=0.7) and 24 (p=0.6) months, respectively. Conclusions: In mchRCC pts, Su tx may have similar outcome to mccRCC pts.
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