No survival advantage with atezolizumab plus bevacizumab in renal cell carcinoma

January 2022 Cancer trials Nalinee Pandey
Human kidney cross section on scientific background

In previously untreated metastatic renal cell carcinoma (mRCC) patients, combination immunotherapy (atezolizumab + bevacizumab) did not improve overall survival (OS) as compared to sunitinib monotherapy. The final OS analysis of the IMmotion151 trial was recently published in the journal JAMA Oncology.

An open-label, multicentre, phase III randomised clinical study enrolled 915 patients (73.1% men and 26.9% female) with previously untreated, mRCC. Patients were randomly assigned to receive either atezolizumab (1200 mg, every three weeks, intravenous) + bevacizumab (15 mg/kg, intravenous, every three weeks) (median age: 62 years) or sunitinib (50 mg orally once daily, four weeks on and two weeks off) (median age: 60 years) to assess the efficacy and safety of the treatment combination. The study’s two primary endpoints were progression-free survival (PFS) in PD-L1+ patients and OS in the intention-to-treat (ITT) population. Additionally, the exploratory analysis included OS in PD-L1+, transcriptomic subtypes, and safety.

Main findings

An earlier analysis of PFS after a median follow up of 15 months has reported a prolonged PFS in the atezolizumab-bevacizumab arm versus sunitinib treatment group (15.0 versus 7.7 months, hazard ratio (HR) 0.74; 95% CI: 0.57-0.96; P=0.0217). However, after a median follow-up of 40 months, a similar OS was observed between atezolizumab-bevacizumab and sunitinib groups in the ITT populations (36.1 versus 35.3 months, respectively; HR: 0.91; 95% CI: 0.76-1.08) as well as in patients with PD-L1+ disease (38.7 versus 31.6 months, respectively; HR: 0.85; 95% CI: 0.64-1.13). While there was no overall difference in OS between both treatment arms, different survival outcomes were observed in subset populations. For instance, patients in the angiogenic subset had a shorter OS with atezolizumab-bevacizumab; it was prolonged in the T-effector/proliferative, proliferative, and snoRNA subsets. Adverse events (grade 3 or 4) were observed in the combination arm (46%), with proteinuria being the most common event (8%). Additionally, 28% and 12% of patients discontinued treatment due to adverse events in the combination and sunitinib arm, respectively.


The results of the study report no differences in the survival outcomes with atezolizumab-bevacizumab versus sunitinib in mRCC patients. However, analysing OS in biomarker defined subsets provided a molecular basis of different survival outcomes.


Motzer RJ, Powles T, Atkins MB, et al. Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma. JAMA Oncol. 2021 Dec 23. Epub ahead of print.