ASCO GU 2018: IMmotion 151: A randomized Phase III Study of Atezolizumab Plus Bevacizumab versus Sunitinib in Untreated Metastatic Renal Cell Carcinoma

San Francisco, CA ( Atezolizumab (anti-PD-L1) and bevacizumab (anti-VEGF) have showed first line anti-tumor activity with an acceptable side effect profile in a Phase II study performed by Dr. McDermott, presented at GU ASCO 2017.  In this oral abstract session, Dr. Motzer presented the first phase III randomized clinical trial combining a PD-L1/PD-1 with an anti-VEGF agent in first line metastatic renal cell carcinoma. It was theorized that atezolizumab’s T cell mediated cancer cell killing may be enhanced through bevacizumab’s reversal of VEGF mediated immunosuppression.

In the IMmotion 151 trial, patients were enrolled who were treatment naïve regardless of MSKCC risk group to atezolizumab 1200mg IV q 3 weeks + bevacizumab 15 mg/kg IV q3 weeks or sunitnib 50mg PO daily 4 week on/2week off.  Patients were stratified by PD-L1 status (<1% vs >1%).  Primary endpoints included progression free survival in PD-L1 positive patients and overall survival in an intention to treat analysis.  Secondary endpoints include progression free survival in an intention to treat analysis and overall survival in PD-L1 positive patients, amongst others.  Patients were included in this study if they had clear cell and/or sarcomatoid histology with a good performance status.  915 patients were included and stratified based upon MSKCC risk score, presence of liver metastasis and PD-L1 IHC status. 

Statistically, a predetermined cutoff date of September 29, 2017 was used.  5% alpha was split into 4% for PFS in PD-L1+ and 1% for OS in the intention to treat population.

Baseline characteristics were comparable between treatment arms and median follow up was 15 months.  In PD-L1+ patients, PFS HR for atezolizumab + bevacizumab versus sunitinib was 0.74 (95% CI 0.57-0.96).  Median PFS was 11.2 months for atezolizumab + bevacizumab compared to 7.7 months for sunitinib (p=0.02).  In the intention to treat analysis, HR was 0.83 (95% CI 0.70-0.97) with median PFS 11.2 months for atezolizumab + bevacizumab compared to 8.4 months for sunitinib.  In the PD-L1+ group, confirmed objective response rates were 43% and 35% for atezolizumab + bevacizumab versus sunitinib, respectively.  Overall survival was immature at this first interim analysis. 

In the PD-L1+ group, PFS benefit was reliable across analyzed subgroups, including MSKCC risk, presence of liver metastases and sarcomatoid histology.  Dr. Motzer stated that the safety profile demonstrates is tolerability with only 40% of atezolizumab + bevacizumab treated patients compared to 54% of sunitinib treated patients had grade 3-4 treatment-related adverse events. Additionally, discontinuation rate was lower with atezolizumab + bevacizumab compared to sunitinib.  The only grade 3-4 adverse events that were more common with atezolizumab + bevacizumab compared to sunitinib was proteinuria. 

In summary, the IMmotion 151 trial met its primary PFS endpoint in the PD-L1 positive patients with atezolizumab + bevacizumab compared to sunitinib with fewer high grade adverse reactions.  This data does support atezolizumab + bevacizumab as first line therapy in metastatic clear cell renal cell.  We look forward for the data to continue to mature to help patient outcomes in this space. 

Presented by: Robert J. Motzer, MD Department of Medical Oncology, Memorial Sloan Kettering Cancer Center

Written by: David B. Cahn, DO, MBS @dbcahn, Fox Chase Cancer Center, Philadelphia, PA at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA
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