Combined treatment with atezolizumab and bevacizumab for untreated metastatic renal cell carcinoma (mRCC) reduces the likelihood of disease progression better than sunitinib, according to study findings presented at the 2018 Genitourinary Cancers Symposium. The benefit appears to be greater in patients with PD-L1 positive tumors.
The phase III study, which began in 2015, enrolled 915 adult patients with mRCC who were randomly assigned to receive either the immunotherapy atezolizumab plus the targeted therapy bevacizumab intravenously every 3 weeks or sunitinib, an orally administered drug, daily for 4 weeks, followed by 2 weeks off treatment. Atezolizumab is an immune checkpoint inhibitor that blocks the PD-L1 protein on tumor cells, thereby allowing the immune system to recognize and attack those cells. Bevacizumab and sunitinib block vascular endothelial growth factor. Of the 915 patients, 362 had PD-L1 positive tumors.
After a median survival follow-up of 15 months, the median PFS for the entire study population was 11.2 months in the atezolizumab-bevacizumab group and 8.4 months among sunitinib recipients. In the PD-L1 positive group, median PFS was 11.2 months in the atezolizumab-bevacizumab group compared with 7.8 months in the sunitinib arm. In the overall study population, patients who received atezolizumab-bevacizumab had a significant 17% decreased risk of progression compared with sunitinib-treated patients (HR = 0.83; 95% CI 0.70, 0.97; P = 0.219). In the PD-L1 positive population, patients in the atezolizumab-bevacizumab group had a 26% decreased risk of progression compared with sunitinib recipients (HR = 0.74; 95% CI 0.57, 0.96; P = 0.0217).
Treatment-related grade 3-4 adverse events occurred less frequently in the atezolizumab-bevacizumab than sunitinib group (40% vs 54%).
“These results support atezolizumab plus bevacizumab as a first-line treatment option for patients with PD-L1 positive advanced RCC,” Dr. Motzer told attendees.
For an aggressive cancer such as mRCC, where less than 20% of patients survive 5 years after diagnosis, a 3.5-month longer PFS, given the tolerability of the combined regimen, is an important development, according to Dr Motzer.
“The study that Dr Motzer presented represents an important breakthrough in kidney cancer therapy,” said Sumanta K. Pal, MD, an American Society of Clinical Oncology (ASCO) expert who moderated a pre-symposium press conference at which Dr Motzer presented the study’s findings. He noted that the combination therapy achieved a higher rate of complete response than sunitinib. “Achieving a complete response … is really the highest bar that we can strive for in this setting,” he said.
The symposium is cosponsored by ASCO, the American Society for Radiation Oncology, and the Society of Urologic Oncology.
This study was funded by F. Hoffmann-La Roche Ltd., Basel, Switzerland.
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). Data presented at the 2018 Genitourinary Cancers Symposium, held in San Francisco Feb. 8-10. Abstract 578.