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Data are limited regarding outcomes in patients with end-stage renal disease (ESRD) and metastatic renal cell carcinoma (mRCC) receiving targeted therapy. We retrospectively identified patients with mRCC and ESRD treated at the University of Texas M.D. Anderson Cancer Center from 2002 to 2012. Fourteen patients were identified with a median number of targeted therapies (TTs) per patient of 3 (range, 1–4). Outcomes in patients with mRCC and ESRD were similar to those reported in patients with normal kidney function. Introduction Limited data are available regarding patients with renal cell carcinoma and ESRD treated with TTs. The objective of this study was to explore the tolerability and safety of TT in patients with mRCC and ESRD. Patients and Methods We retrospectively identified patients with mRCC and ESRD treated at the University of Texas M.D. Anderson Cancer Center from 2002 to 2012. Patient characteristics including demographic, histology, treatment, and adverse events are reported. Duration of treatment (TOT) was determined from date of drug initiation to discontinuation. Overall survival (OS) was determined from initiation of TT to death. Statistics are descriptive. Results Fourteen patients were identified. Ten patients had clear-cell histology and 4 had papillary histology. The median number of TTs per patient was 3 (range, 1–4) with median TOT of 28 months for all TTs. Eighty-eight percent of all toxicities were Grade 1 to 2; no Grade 4 toxicities were noted. Treatment discontinuations included 3 patients treated with sorafenib due to hand-foot syndrome, intolerable fatigue, and squamous cell skin cancer development; 2 patients treated with pazopanib due to intolerable fatigue and increased transaminase levels; and 1 patient treated with everolimus due to pneumonitis. Eight patients died from progressive disease. Median OS from initiation of TT was 28.5 months and 35 months from time of diagnosis. Conclusion Toxicities were mild to moderate and consistent with those reported in previous studies. TTs appear to be safe, well tolerated and produce antitumor response in patients with mRCC and ESRD receiving dialysis.

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213 Background: Previous reports on mutations in the isocitrate dehydrogenase 1 (IDH1) gene in prostate cancer focused on the evolutionarily conserved residue R132 located in the substrate binding site of IDH1. One study reported R132 mutations in 2/75 (2.7%) prostate cancers, whereas the other study did not find R132 mutation in 4 prostate cancers. We therefore studied the IDH1 mutations in our prostate cancer targeted exon sequencing database. Methods: Targeted exon sequencing was performed on 52 treatment naïve prostate cancers as part of Moffitt Cancer Center’s Total Cancer Care initiative. The coverage was set to be at least 50 fold. 51/52 samples are primary prostate cancer obtained during radical prostatectomy and 1 sample is a brain metastasis. The 1000 Genomes and the NHLBI Exome Sequencing Project (ESP) were used to exclude likely polymorphisms. The catalogue of somatic mutations in cancer (COSMIC) was used to identify mutations seen in other sequencing projects, and Polyphen2 was used to predict the potential detrimental effect of the amino acid changes predicted from the genetic mutations. Results: 1/51 (2%) primary prostate cancers harbor the R132H mutation, which is known to generate the oncometabolite, (R)-2-hydroxylutarate. Y183C was identified in 1/51 samples. This amino acid change in exon 6 of IDH1 is seen at 1% allele frequency in 1000 Genomes and ESP-euro. It is classified as "probably_damaging" with a PolyPhen2 score of .999. Another "probably_damaging" amino acid change is T325M mutation, which is identified in a different primary prostate cancer. V178I in IDH1 was also identified and is thought to be an inherited variant, given it has an allele frequency of 4% in 1000 Genomes, 5% in ESP-european, and 8% in ESP-African-American. Among the frequent gene mutations in metastatic prostate cancer, only a missense mutation in the androgen receptor (H875Y) was identified in the treatment naïve brain metastasis. This H875Y has been linked to promiscuous androgen receptor. Conclusions: Mutations in IDH1 R132H and other “probably_damaging” amino acid changes are identified in primary prostate cancers. This holds further implications for future studies on prostate cancer, and may point to an interesting target in the disease.