A Phase II, Randomized Study of Atezolizumab (Anti PD-L1 Antibody) Administered as Monotherapy or in Combination with Bevacizumab Versus Sunitinib in Participants with Untreated Advanced Renal Cell Carcinoma

Status: 
Open
Sponsor: 
Hoffmann-La Roche
Enrollment: 
305
Study Design: 
This multicenter, randomized, open-label study evaluated the efficacy, safety and tolerability of atezolizumab as monotherapy or in combination with bevacizumab versus sunitinib in patients with histologically confirmed, previously untreated mRCC. After progression on atezolizumab or sunitinib, crossover to combination arm atezolizumab + bevacizumab was allowed.
Rationale: 
VEGF pathway inhibition has significantly improved the outcome of patients with advanced or metastatic renal cell carcinoma (mRCC), however most patients will develop resistance, often within 12 months. Therefore, new therapeutic strategies are needed to reach durable responses. Combination of immune checkpoint inhibitors with VEGF inhibitors may prevent the development of resistance.
Endpoints: 
Primary Endpoint: progression free survival (PFS) according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 measured in both Intent-to-Treat (ITT) Population and subjects who have detectable PD-L1 expression. Secondary Endpoints include overall response rate (ORR) per RECIST 1.1, duration of response (DoR), overall survival (OS) and safety profiles of the different treatment arms.
Results: 
More than 50% of patients were PD-L1+. In the overall population, PFS was 11.7; 6.1 and 8.4 months in the combination atezolizumab + bevacizumab; atezolizumab monotherapy and sunitinib group respectively. In the PD –L1 + group, PFS reached 14.7 months (95% CI 8.2- 25.1, HR 0.64) with the combination therapy. Overall response rate was 32%, 25% and 29% in the combination arm, atezolizumab monotherapy and sunitinib group respectively. Upon progression in the monotherapy arms, 78% of the sunitinib and 60% of the atezolizumab patients subsequently crossed over to the combination arm with atezolizumab + bevacizumab and achieved ORRs of 28% and 24%, respectively. Safety data in all arms was comparable to the already known individual treatment profiles.
Comments: 
PD-L1 inhibitor atezolizumab with bevacizumab showed promising antitumor activity in treatment naïve mRCC patients. Checkpoint inhibitors in combination with VEGF inhibitors may become a key component of the treatment options for mRCC. A phase III study of first line atezolizumab in combination with bevacizumab versus sunitinib is currently ongoing (NCT02420821).