A score 1% was used to determine positivity (yes no).14-16 Statistical Analysis Patients who received at least 1 dose of either study treatment were included in the analysis. for 36 patients; 15 (42%) had 1% expression on tumor cells. ORR in PD-L1Cpositive patients was 60% (n = 9) 19% (n = 4) in PD-L1Cnegative patients. Eight patients (13%) developed treatment-related grade 3 toxicities. There were no treatment-related grade 4-5 toxicities. QOL was maintained throughout therapy. CONCLUSION In Fst this study, atezolizumab and bevacizumab demonstrated safety and resulted in objective responses in patients with variant histology RCC or RCC with 20% sarcomatoid differentiation. This regimen warrants additional exploration in patients with rare RCC, particularly those with PD-L1Cpositive tumors. INTRODUCTION Although conventional clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, up to 20% of all RCC cases are classified under the broad category of non-ccRCC or, more recently, categorized as rare histologic variants. This is a diverse group of malignancies that includes papillary, chromophobe, medullary, collecting duct, TFE3 translocation, and unclassified RCC. Each subtype is driven by a unique pathogenesis that in some cases is not fully understood, which likely accounts for the differing clinical presentation and response to therapy of these rare histologic variants. In addition, any RCC histology may be associated with sarcomatoid differentiation.1-3 Several large series have demonstrated that patients with variant histology RCC or RCC with sarcomatoid differentiation have a worse prognosis with lower response rates to targeted therapies than their counterparts with ccRCC or those who lack sarcomatoid differentiation, which underscores the need for improved treatments for these individuals.3-6 Given its heterogeneous nature, this group of diseases has historically been excluded from large phase III studies, which have focused primarily on patients with ccRCC (or component of clear cell features). Current management guidelines for patients with variant histology RCC are based on extrapolation of data from patients with ccRCC, smaller phase II trials that demonstrated superiority of sunitinib over everolimus,7,8 and subgroups analyses from phase III trials. While immunotherapy combinations have evolved as frontline regimens in clear cell histology, given their proven superiority over sunitinib in patients with ccRCC, sunitinib remains a preferred regimen by guideline panels for the initial management of variant histology RCC.9 The combination of bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF) A, and atezolizumab, a monoclonal antibody targeting programmed death-ligand 1 (PD-L1), has only been studied in patients with ccRCC. Data from the phase I study of the combination suggested improvement in antitumor immunity given enhanced T-cell infiltration and decreased myeloid immunosuppression with the addition of bevacizumab to atezolizumab.10 The combination was further studied in patients with advanced ccRCC in phase II and III studies that showed enhancing antitumor activity with a favorable toxicity profile.10,11 We therefore conducted a multicenter, investigator-initiated, prospective phase II study of atezolizumab plus bevacizumab in patients with advanced variant histology RCC or RCC with at least 20% sarcomatoid differentiation. PATIENTS AND METHODS Patient Population This study enrolled patients with histologically confirmed advanced variant histology RCC, including papillary, chromophobe, collecting duct, medullary, translocation, and unclassified RCC with or without sarcomatoid differentiation, in addition to ccRCC histology with 20% sarcomatoid differentiation. Pathology review conducted by a genitourinary pathologist was required at each institutional site to confirm histology. Advanced disease was defined as unresectable, locally recurrent, or metastatic by American Joint Commission on Cancer seventh edition staging system. Patients could have received any number of prior regimens provided that they had not received bevacizumab or any PD-1/PD-L1 inhibitors. Patients were required to have measurable disease per RECIST version 1.1, Eastern Cooperative Oncology Group performance status 2, adequate organ function, and controlled blood pressure. Patients with active brain metastases, active autoimmune disease, or a condition that required treatment with prednisone 10 Forsythoside A mg/d or equivalent were excluded. The study enrolled subjects at the Dana-Farber Cancer Institute; Beth Israel Deaconess Medical Center; University of California, San Diego, Moores Cancer Center; and Karmanos Cancer Center. The study was approved by the institutional review board at each participating institution. All patients provided written informed consent. Study Design Before initiation of therapy in this multicenter, phase II, open-label, single-arm study, patients underwent a baseline tumor biopsy, unless medically not feasible. Eligible patients received treatment with Forsythoside A atezolizumab (1,200 mg) and bevacizumab (15 mg/kg) intravenously every 3 weeks. Dose modifications were not permitted; however, Forsythoside A dose delays were allowed. If 1 agent was discontinued, continuation of the other agent alone.