[PubMed] [Google Scholar] 12. including cases of papillary (= 3), chromophobe (= 2), unclassified (= 3) RCC, and ccRCC with sarcomatoid features (= 1). No tumor shrinkages were observed for patients with collecting duct or translocation-associated RCC. Conclusions Curcumol A subset of patients with nonclear-cell and sarcomatoid variant ccRCC subtypes benefit from mTOR inhibitors, but most have poor outcome. Histologic subtype does not appear to be helpful in selecting patients for rapalog therapy. Future efforts should include the identification of predictive tissue biomarkers. (= 85) (%)6 (7)3 (13)3 (5)SD, (%)40 (49)7 (30)33 (56)PR or SD 6 months, (%)20 (24)4 (17)14 (24)PD, (%)36 (44)13 (57)23 (39) Open in a separate window PD, progressive disease; PR, partial response; SD, stable disease. Open in a separate window Figure 1. Duration of mammalian target of rapamicin inhibitor treatment of patients with sarcomatoid clear-cell RCC (A) and nonclear-cell RCC (B) according to histologic subtypes. Each bar represents an individual patient. Line pattern/color distinguishes best response by RECIST. Median PFS for the entire cohort, for patients with ncRCC, and for those with sarcomatoid ccRCC was 2.9 months [95% confidence interval (CI) 1.8C4.3], 2.8 months (95% CI 1.8C4.2), and 3.5 months (95% CI 1.6C5.4), respectively (Table ?(Table3;3; Figure ?Figure2).2). For treatment-na?ve ncRCC patients (= 27), the median PFS with rapalogs was 3.8 months (95% CI ?2.2C6.8), whereas pretreated patients showed a Curcumol median PFS of 2.7 months (95% CI 1.6C5.1). Nine patients (10%) received rapalogs for 1 year (range 13.3C37.8 months), including cases of papillary (= 3), chromophobe (= 2), unclassified (= 3), and sarcomatoid ccRCC (= 1). With a median follow-up of 33 months, the median OS for the entire cohort, for patients with ncRCC, and for those with sarcomatoid ccRCC was 8.7 months (95% CI 6.5C12.0), 9.1 months (95% CI 6.5C12.6), and 8.2 months (95% CI 4.8C14.3), respectively (Table ?(Table3;3; Figure ?Figure2).2). Across the entire cohort, the median survival differed significantly when stratifying patients by MSKCC risk group  (9.3, 9.0, and 6.4 months for patients with favorable, intermediate, and poor risk, respectively; = 0.04; see Figure ?Figure33). Table 3. Progression-free survival and overall survival according to histology = 10) with a median OS of 13.2 months [9, 10]. A phase II trial of everolimus in advanced ncRCC enrolled 49 patients of various ncRCC subtypes, the majority of which were pretreated, and reported a median OS and PFS of 14 and 5.2 months, respectively . Although the authors noted a trend for a longer PFS in chromophobe RCC, the small number of patients (= 8) and lack of Curcumol statistical significance (= 0.084) do not allow definitive conclusions. The recently reported RCC expanded access trial for everolimus, included 75 patients with metastatic ncRCC and reported an overall response rate of 1 1.3% and a median treatment duration of 12 weeks for this group . Curcumol In our study, we report outcome data with mTOR inhibitors in patients with advanced sarcomatoid ccRCC, again with varying degrees of therapeutic benefit (Figure ?(Figure1).1). A defined standard of care for this group Curcumol of patients has not been established. None of the pivotal trials leading to the approval of targeted therapeutics in RCC assessed presence of sarcomatoid differentiation by central pathology. Previously published retrospective series suggest that VEGF inhibitors can be effective for some sarcomatoid patients [7, 17]. Case reports have previously suggested that treatment benefit from rapalogs in sarcomatoid ccRCC varies . We found similar heterogeneity across our cohort, which is, to our knowledge, the largest group of patients with sarcomatoid ccRCC treated with rapalog therapy reported to date. Overall, Rabbit Polyclonal to Cox1 patients responded poorly, with 50%.