Results of a Multicenter Phase II Study of Atezolizumab and Bevacizumab for Patients With Metastatic Renal Cell Carcinoma With Variant Histology and/or Sarcomatoid Features

Abstract

PURPOSE In this multicenter phase II trial, we evaluated atezolizumab combined with bevacizumab in patients with advanced renal cell carcinoma (RCC) with variant histology or any RCC histology with ≥ 20% sarcomatoid differentiation. PATIENTS AND METHODS Eligible patients may have received previous systemic therapy, excluding prior bevacizumab or checkpoint inhibitors. Patients underwent a baseline biopsy and received atezolizumab 1,200 mg and bevacizumab 15 mg/kg intravenously every 3 weeks. The primary end point was overall response rate (ORR) by RECIST version 1.1. Additional end points were progression-free survival (PFS), toxicity, biomarkers of response as determined by programmed death-ligand 1 (PD-L1) status, and on-therapy quality-of-life (QOL) metrics using the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 and the Brief Fatigue Inventory. RESULTS Sixty patients received at least 1 dose of either study agent; the majority (65%) were treatment naïve. The ORR for the overall population was 33% and 50% in patients with clear cell RCC with sarcomatoid differentiation and 26% in patients with variant histology RCC. Median PFS was 8.3 months (95% CI, 5.7 to 10.9 months). PD-L1 status was available for 36 patients; 15 (42%) had ≥ 1% expression on tumor cells. ORR in PD-L1–positive patients was 60% (n = 9) v 19% (n = 4) in PD-L1–negative 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 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-L1–positive tumors.

Outcomes With First-Line PD-1/PD-L1 Inhibitor Monotherapy for Metastatic Renal Cell Carcinoma (mRCC): A Multi-Institutional Cohort

“…Combination regimens containing ICIs became the standard of care for patients with mRCC based on phase 3 clinical trials conducted mainly in clear cell tumors (17). The same or similar combinations are being investigated in nonclear cell histologies, and emerging data are promising (18). Yet, not all patients will be considered eligible for those regimens.…”

A Randomized Phase IIa Trial with Temsirolimus versus Sunitinib in Advanced Non-Clear Cell Renal Cell Carcinoma: An Intergroup Study of the CESAR Central European Society for Anticancer Drug Research-EWIV and the Interdisciplinary Working Group on Renal Cell Cancer (IAGN) of the German Cancer Society

“…Individual case reports and the subgroup analysis of the ipili­mumab plus nivolumab and axitinib plus pembrolizu­mab pivotal studies show a promising response in nccRCC and especially those with sarcomatoid features [11, 20-22]. Initial data are also available for the combination of bevacizumab and atezolizumab [23]. The current ESMO guidelines therefore consider the IO/IO combination to be a good therapy option for sarcomatoid RCCs [24].…”

Identification of clinical combination therapies to induce durable responses in kidney cancers

“…NCCRCC accounts for ~20% of kidney cancer, with papillary, chromophobe and sarcomatoid variants accounting for the majority of subtypes 5 .For advanced NCCRCC, the only treatment options, which have been largely extrapolated from agents studied in CCRCC, include antiangiogenics or mTOR inhibitors. However, several large studies have demonstrated that patients with NCCRCC have a worse prognosis with lower response rates to these therapies [9][10][11][12][13][14][15][16] .…”

“…papillary, chromophobe, sarcomatoid) have an intact VHL gene, and are broadly classified as non-clear cell RCC (NCCRCC). NCCRCC show minimal responses to antiangiogenics and have no effective treatment options [9][10][11][12][13][14][15][16] .While recent advances in immunotherapeutic approaches have further improved outcomes for metastatic CCRCC, standard therapies for advanced NCRRCC are lacking and long-term survival is poor 4 .…”