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