Combination atezolizumab and bevacizumab did not improve overall survival (OS), compared with sunitinib monotherapy, in patients with previously untreated, metastatic renal cell carcinoma (RCC), according to the final OS analysis of the IMmotion151 trial published in JAMA Oncology.1

Researchers said they “do not have a clear explanation” for the lack of OS benefit with atezolizumab and bevacizumab. Prior results from IMmotion151 showed improved progression-free survival (PFS) with the combination.2

The phase 3 trial (ClinicalTrials.gov Identifier: NCT02420821) included 915 patients with previously untreated, metastatic RCC. The patients were randomly assigned to atezolizumab plus bevacizumab or sunitinib.

The mean age was 62 years for patients receiving atezolizumab-bevacizumab and 60 years for patients receiving sunitinib. In the entire population, 73.1% of patients were men.


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The study’s coprimary endpoints were PFS in patients with PD-L1-positive disease and OS in the intention-to-treat population. In the prior analysis, the median follow-up for PFS was 15 months. In the PD-L1-positive population, the median PFS was 11.2 months in the atezolizumab-bevacizumab arm and 7.7 months in the sunitinib arm (hazard ratio [HR], 0.74; 95% CI, 0.57-0.96; P =.0217).

The final OS analysis had a minimum follow-up of 40 months. OS was similar between the treatment arms. The median OS was 36.1 months with atezolizumab-bevacizumab and 35.3 months with sunitinib (HR, 0.91; 95% CI, 0.76-1.08).

The OS results were similar between the treatment arms for patients with PD-L1-positive disease as well. The median OS was 38.7 months with atezolizumab-bevacizumab and 31.6 months with sunitinib (HR, 0.85; 95% CI, 0.64-1.13).

In the previous analysis, the researchers identified 7 molecular subsets of patients with distinct gene expression profiles. For the current analysis, the researchers evaluated OS in these molecular subsets.

Patients in the angiogenic subset had shorter OS with atezolizumab-bevacizumab than with sunitinib. In contrast, atezolizumab-bevacizumab was associated with prolonged OS for the T-effector/proliferative, proliferative, and snoRNA subsets.

“While the combination of atezolizumab pus bevacizumab did not show improved OS vs sunitinib, the biomarker analyses provide insight into the molecular basis of different survival outcomes,” the researchers wrote.

The rate of grade 3-4 treatment-related adverse events was 46% in the atezolizumab-bevacizumab arm. The most common of these events was proteinuria (8%).

The proportion of patients who discontinued treatment due to adverse events was 28% in the combination arm and 12% in the sunitinib arm.

Disclosures: This research was supported by F. Hoffmann-La Roche Ltd. and Genentech, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References

  1. 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. Published online December 23, 2021. doi:10.1001/jamaoncol.2021.5981
  2. 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. Lancet. 2019;393(10189):2404-2415. doi:10.1016/S0140-6736(19)30723-8