ESMO 2018: Safety and Tolerability of Atezolizumab plus Bevacizumab vs Sunitinib in Untreated Metastatic Renal Cell Carcinoma: IMmotion 150 and IMmotion 151

Munich, Germany ( IMmotion 150 (Phase II) compared the efficacy of atezolizumab (atezo) plus bevacizumab (bev) with atezolizumab alone and sunitinib alone and then allowed for crossover in the latter 2 arms to atezolizumab plus bevacizumab.1 IMmotion 151  (Phase III) compared the efficacy of atezolizumab plus bevacizumab vs sunitinib for first-line therapy of metastatic renal cell carcinoma2.

The rationale for this combination is that bevacizumab may be able to reverse VEGF-mediated immunosuppression, thereby enhancing atezolizumab’s T cell-mediated cancer cell-killing effect. In IMmotion 150, the overall response rate in the atezo+bev arm was 32% (32/101) in the intention to treat arm and 46% in the PD-L1+ arm. atezo+bev PFS was 11.7 months compared with 8.4 months for sunitinib – this difference was not statistically significant.  However, in the larger phase III trial (IMmotion 151), atezo+bev improved progression-free survival in both the PD-L1+ positive population (as defined by ≥1% IC using SP142 assay) and intention to treat cohort.  These two studies suggest that atezolizumab plus bevacizumab may be a reasonable first-line therapy in select patients with advanced RCC.

ESMO 2018 IMmotion 150 chart

This study pools the patients from IMmotion 150 and IMmotion151 and carefully examines the safety data. The combined cohorts include 552 patients treated with atezo+bev and 546 patients treated with sunitinib. The baseline characteristics of each cohort were similar, with respect to age, sex, performance status, MSKCC risk, liver metastases, PD-L1 expression, and histology.

Similar numbers of treatment-related events occurred in both cohorts (91% for atezo+bev and 96% for sunitinib). More patients reported grade 3/4 treatment-related events with sunitinib (54%) compared with atezo+bev (40%). More patients discontinued therapy due to treatment-related adverse events on sunitinib (8%) than on atezo+bev (5%). For patients on atezo+bev, corticosteroids were needed to manage immune toxicity in 16% of patients. 

ESMO 2018 TRAEs summary

ESMO 2018 common TRAEs

This study demonstrates that the combination of atezo+bev has a safety profile comparable to sunitinib and is tolerated by most patients. Most patients did not experience immune toxicities requiring corticosteroids for management. This study gives further evidence that atezo+bev may be a reasonable first-line option for patients with mRCC.

Presented By: Cristina Suarez,MD, Medical Oncology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Oncology, Barcelona, Spain

Written By: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, Twitter: @TheRealJasonZhu at the 2018 European Society for Medical Oncology Congress (#ESMO18), October 19-23,  2018, Munich Germany

1. Atkins MB, McDermott DF, Powles T, et al. IMmotion150: A phase II trial in untreated metastatic renal cell carcinoma (mRCC) patients (pts) of atezolizumab (atezo) and bevacizumab (bev) vs and following atezo or sunitinib (sun). Journal of Clinical Oncology 2017;35:4505-.
2. Motzer RJ, Powles T, Atkins MB, et al. IMmotion151: A Randomized Phase III Study of Atezolizumab Plus Bevacizumab vs Sunitinib in Untreated Metastatic Renal Cell Carcinoma (mRCC). Journal of Clinical Oncology 2018;36:578-.