ASCO 2019: Atezolizumab + Bevacizumab Versus Sunitinib in Patients with Untreated Metastatic Renal Cell Carcinoma and Sarcomatoid Histology: IMmotion151 Subgroup Analysis - Medical Oncologist Perspective

Chicago, IL (UroToday.com) IMmotion 151 was a randomized phase III study evaluating atezolizumab plus bevacizumab versus sunitinib for patients with mRCC with either clear cell or sarcomatoid histologies. 915 patients were enrolled and 40% of patients had PD-L1 positive disease. After a median of 24 months follow up, the median progression-free survival (PFS) was 11.2 months in the atezolizumab plus bevacizumab group, compared to 7.7 months in the sunitinib group.1 In terms of overall survival (OS), there was no significant difference in the intention to treat analysis - median overall survival had a hazard ratio (HR) of 0.93 (95%CI 0.76–1.14). This abstract focuses on the subgroup of patients with sarcomatoid features on histology.

ASCO2019_key_eligibility.png

A total of 142 patients (16%) from IMmotion 151 had tumors with some component of sarcomatoid histology. Baseline characteristics are below.

ASCO2019 table1 characteristics

In the sarcomatoid population, the objective response rate was significantly higher for patients receiving atezo/bev than sunitinib (49% vs 14%) and the CR rate was 10% in the atezo/bev arm compared with 3% in the sunitinib arm. This CR rate is comparable to the CR rate seen with Pembro/Axi in Keynote 426 (as described during ASCO 2019 (Abstract 4500)) and data from the ipi/nivo sarcomatoid cohort also shows a very impressive CR rate at (18%).2 Gene expression profiles demonstrated higher T-effector gene expression in sarcomatoid vs non-sarcomatoid (54% vs 40%) and PD-L1+ was more common in sarcomatoid as well (63% vs 39%).

ASCO2019 efficacy summary

In terms of overall survival, patients with sarcomatoid features had increased OS with atezo+bev vs sunitinib, regardless of PD-L1 status.

ASCO2019 survival

Biomarker data revealed that patients with sarcomatoid features had a higher percentage of Angiolow expression (66%) compare with patients with non-sarcomatoid features (35%) and patients with sarcomatoid features also had a higher rate of PD-L1 expression (63%) compared with non-sarcomatoid tumors (39%).

ASCO2019_angiogenesis.png

Patients with mRCC with sarcomatoid features had improved survival, objective response rate, and progression-free survival with combination atezolizumab/bevacizumab compared with sunitinib. Combination tyrosine kinase inhibitor (TKI) and checkpoint inhibitor is now a proven strategy for patients with mRCC, with both axitinib/avelumab and pembrolizumab/avelumab approved in the United States. This data shows that for patients with mRCC with sarcomatoid features, atezo/bev shows similar efficacy compared to the other two options. However, without an OS benefit for all patients, at this time, this combination is unlikely to be chosen as a frontline therapy for patients with mRCC.

Presented by: Brian I. Rini, MD, FACP, Hematology and Medical Oncology, Cleveland Clinic Main Campus, Cleveland, OH

Written by: Jason Zhu, MD, Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA

References:
  1. Rini BI, Powles T, Atkins MB, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. The Lancet 2019.
  2. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. New England Journal of Medicine 2018;378:1277-90.
  3. Rini BI, Powles T, Atkins MB, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. The Lancet 2019.
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