Outcomes with novel combinations in non-clear cell renal cell carcinoma(nccRCC): ORACLE study.

4580 Background: Despite advances in the treatment of clear cell RCC, there is a paucity of data to guide management of nccRCC due to the heterogeneity and rarity of these tumors. The clinical activity of new combination therapies (including immunotherapy (IO), anti-vascular endothelial growth factor inhibitors (VEGF), and mammalian target of rapamycin (mTOR) inhibitors) in metastatic nccRCC is not known. Methods: In this multicenter retrospective analysis, we explored the efficacy of combination systemic therapies in patients with nccRCC. Baseline and follow-up demographic, clinical, treatment, and radiographic data were collected. The primary endpoint was objective response rate (ORR) assessed by investigator review. Secondary endpoints include progression- free survival (PFS), disease control rate (DCR), median duration of response (DOR), overall survival (OS), and biomarker correlates. Results: Among 66 included patients, median age was 59 yr; 60% were male and 62% white. Histologies included papillary (38%), chromophobe (17%), unclassified (24%), translocation (12%), and other (9 %). Sarcomatoid and/or rhabdoid differentiation was present in 18%, 70% had prior nephrectomy, 86% were IMDC intermediate/poor risk, 29% and 32% had liver and bone metastasis respectively. 67% received combination treatment in the first line. Comparison of outcomes based on treatment regimen is shown in the table. Conclusions: Antitumor activity was observed with novel combinations in nccRCC which warrants further prospective studies. Response rates and survival with combination therapy in this dataset remain inferior to rates seen in clear cell RCC.[Table: see text]

Epithelial-Myoepithelial Carcinoma of the Breast with Rhabdoid Features

Epithelial-myoepithelial carcinoma of the breast is a rare biphasic tumor composed of intermixed malignant epithelial and myoepithelial components. Myoepithelial cells are known to adopt varied morphologies, including spindle, chondroid, clear cell, and rhabdoid morphologies, and can represent a diagnostic challenge when isolated on biopsy. Rhabdomyosarcoma, phyllodes tumor, metaplastic carcinoma, and myoepithelial carcinoma are primary breast tumors that all have been shown to exhibit rhabdoid features, whether representing true differentiation or morphological mimic. We here report an epithelial-myoepithelial carcinoma of the breast with rhabdoid features in a 76-year-old woman. The rhabdoid-appearing myoepithelial cells are negative for myogenin, consistent with a rhabdoid-like morphology rather than a true rhabdoid differentiation, comparably to previously described myoepithelial carcinoma with rhabdoid features. To our knowledge, this is the first reported case of epithelial-myoepithelial carcinoma of the breast with rhabdoid features and thus adds another entity to the differential diagnosis of breast lesions with rhabdoid features.