2017 GU Cancers Symposium: Atezolizumab Plus Bevacizumab Shows Potential in Metastatic Renal Cell Carcinoma
Results from the phase II IMmotion150 study that compared atezolizumab (Tecentriq) plus bevacizumab (Avastin) and atezolizumab monotherapy to sunitinib (Sutent) alone in patients with previously untreated, locally advanced or metastatic renal cell carcinoma were presented at the 2017 Genitourinary Cancers Symposium in Orlando, Florida (Abstract 431).
IMmotion150 is the first randomized clinical trial to evaluate the combination of atezolizumab and bevacizumab in advanced renal cell carcinoma. The study was designed to inform further clinical development of this combination, and these study results reinforce the potential of the combination in this setting.
The study showed that patients whose disease expressed programmed cell death ligand 1 (PD-L1) and were treated with atezolizumab plus bevacizumab had a 36% reduction in the risk of the disease worsening or death compared to people treated with sunitinib alone (median progression-free survival = 14.7 vs 7.8 months; hazard ratio [HR] = 0.64; 95% confidence interval [CI] = 0.38–1.08). No progression-free survival advantage was observed compared to sunitinib in the intention-to-treat population (median = 11.7 vs 8.4 months; HR = 1.00; 95% CI = 0.69–1.45).
Median duration of response has not yet been reached after 20.7 months of follow-up across treatment arms. Adverse events in the atezolizumab-plus-bevacizumab arm were consistent with those observed in previous studies of each drug.
“These phase II results support the scientific rationale for potentially combining atezolizumab and bevacizumab in people with this type of kidney cancer,” said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development at Genentech. “There is a significant need for new treatment options for people living with advanced renal cell carcinoma, a disease where currently only about 1 in 10 people are alive beyond 5 years following diagnosis.”
Genentech is also evaluating atezolizumab plus bevacizumab compared to sunitinib in a phase III study (IMmotion151; NCT02420821) in patients with previously untreated, locally advanced, or metastatic renal cell carcinoma. A study of atezolizumab as adjuvant treatment for renal cell carcinoma began enrolling earlier this year.
About the IMmotion150 Study
IMmotion150 is a global, multicenter, open-label, randomized phase II study that was designed to evaluate the efficacy and safety of atezolizumab plus bevacizumab (arm A), atezolizumab alone (arm B), or sunitinib alone (arm C) in 305 patients with previously untreated, locally advanced or metastatic renal cell carcinoma.
People in arm A received atezolizuamb administered intravenously at 1,200 mg every 3 weeks (6-week cycles) plus bevacizumab intravenously at 15 mg until disease progression or lack of clinical benefit. People in arm B received atezolizumab alone (until disease progression or lack of clinical benefit), and people in arm C received sunitinib at 50 mg orally daily for 4 weeks followed by 2 weeks’ rest until disease progression.
The coprimary endpoints were progression-free survival per Response Evaluation Criteria in Solid Tumors, version 1.1 via independent review facility assessment in all randomized patients (intent-to-treat population) and in the PD-L1–selected subgroup. PD-L1 expression was assessed on tumor-infiltrating immune cells with an investigational immunohistochemistry test based on the SP142 antibody being developed by Roche Tissue Diagnostics.
Secondary endpoints included independent review facility–assessed overall response rate and duration of response; investigator-assessed progression-free survival, overall response rate, duration of response, and safety; and overall survival. A summary of the efficacy data from arms A, B and C of the IMmotion150 study can be found here.
IMmotion150 was designed with planned crossover. Over three-quarters (78%) of people receiving sunitinib (arm C) who had disease progression subsequently received atezolizumab plus bevacizumab (arm A). Overall survival results were immature at the time of analysis, with only 35% of events having occurred.
Safety in the atezolizumab plus bevacizumab arm appeared consistent with the known safety profile of the individual drugs. No new safety signals were identified. Frequency of all-grade treatment-related adverse events was similar between arms. The most common adverse events occurring in more than 20% of people receiving atezolizumab plus bevacizumab and with a greater than 5% increase when compared to sunitinib included arthralgia (38%), proteinuria (36%), epistaxis (28%), and pruritus (22%).
Frequency of grade 3–4 adverse events regardless of relationship to treatment were similar between people treated with atezolizumab plus bevacizumab (63%) and sunitinib (69%). Treatment-related grade 3–4 events were reported in 40% of people treated with atezolizumab plus bevacizumab and in 57% of people treated with sunitinib. One person who was treated with atezolizumab plus bevacizumab experienced intracranial hemorrhage that led to death. Of 101 people, 15 (15%) treated with atezolizumab plus bevacizumab discontinued treatment for adverse events.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
