Atezolizumab plus Bevacizumab Combo Shows Promise in Patients with Metastatic Kidney Cancer

Phoebe Starr

June 2017, Vol 8, No 3 - Immunotherapy


Orlando, FL—Atezolizumab plus bevacizumab showed encouraging responses as a first-line treatment of metastatic renal-cell carcinoma in a phase 2 trial. Although the trial failed to meet its primary end point of significant improvement in progression-free survival (PFS) compared with sunitinib, the combination did reduce the risk for death or disease progression by 36% in patients with elevated PD ligand 1 (PD-L1) expression. The median PFS was almost double in the PD-L1–positive group with atezolizumab plus bevacizumab versus sunitinib (14.7 months vs 7.8 months, respectively).

The results were reported at the 2017 Genitourinary Cancers Symposium by Thomas Powles, MBBS, MRCP, MD, Clinical Professor of Genitourinary Oncology (HCC), Barts Cancer Institute, England.

“Results were impressive in PD-L1–positive patients. This benefit of atezoliz­umab plus bevacizumab in the PD-L1–positive patients is different from what was found with nivolumab, and shows the importance of the biomarker in patients treated with atezolizumab. The combination of atezolizumab plus bevacizumab looks attractive in PD-L1–positive patients, and the PD-L1 biomarker seems particularly marked with the combination,” said Dr Powles. “We could have predicted that the biomarker would be less important with the combination than with atezolizumab monotherapy, but that isn’t what happened.”

“This study is teaching us how to design and conduct our clinical trials in the future,” he stated.

The hypothesis-generating study was the first to evaluate first-line immunotherapy against the benchmark (ie, sunit­inib), and the first study of first-line, targeted therapy against the benchmark.

The phase 2 trial randomized 305 patients with metastatic renal-cell carcinoma in a 1:1:1 ratio to standard-of-care sunitinib versus atezolizumab monotherapy versus atezolizumab plus bevacizumab. Crossover to the combination-therapy arm was allowed following disease progression. Both atezoliz­umab-containing arms were compared with sunitinib.

In the overall intention-to-treat analysis, there was no significant difference in PFS for atezolizumab versus sunitinib or atezolizumab plus beva­cizumab versus sunitinib.

However, a striking difference was observed in PD-L1–positive patients: a 36% reduction in risk for death or disease progression favoring the combination. In PD-L1–positive patients, median PFS was 5.5 months for atezolizumab, 7.8 months for sunitinib, and 14.7 months for the combination.

At the time of data collection, 75% of patients responded to immunotherapy. In PD-L1–positive patients, the overall response rate was 46% for the combination and 28% for atezolizumab alone.

Tolerability was improved in the immunotherapy arms versus sunitinib. Fewer all-cause adverse events, but more immune-related adverse events, were reported in the combination arm versus sunitinib.

At disease progression, 78% of the sunitinib group and 60% of the atezo­lizumab group crossed over to the combination arm. Analysis of crossovers will be presented in the future.

The phase 2 study led to an ongoing phase 3 trial called IMmotion151 to evaluate the combination of atezolizu­mab plus bevacizumab as frontline treatment of metastatic renal-cell carcinoma in PD-L1–positive patients.