Dual Immunotherapy Active vs Sunitinib for PD-L1+ Advanced RCC

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Atezolizumab (Tecentriq) combined with bevacizumab (Avastin) demonstrated antitumor activity compared with sunitinib as first-line therapy.
Atezolizumab (Tecentriq) combined with bevacizumab (Avastin) demonstrated antitumor activity compared with sunitinib as first-line therapy.

ORLANDO, FL Atezolizumab (Tecentriq) combined with bevacizumab (Avastin) demonstrated antitumor activity compared with sunitinib as first-line therapy among patients with PD-L1-positive, locally advanced, or metastatic renal cell carcinoma (RCC), according to a study presented at the 2017 Genitourinary Cancers Symposium.1

Although VEGF inhibition improves outcomes for patients with metastatic RCC, many patients develop resistance to VEGF tyrosine kinase inhibitors, often within the first year of therapy. Researchers evaluated combined VEGF and PD-L1 blockade compared with PD-L1 inhibition alone and VEGF inhibition alone among newly diagnosed patients with metastatic RCC.

The phase 2 IMmotion 150 trial (ClinicalTrials.gov Identifier: NCT01984242) enrolled 305 patients with previously untreated, locally advanced or metastatic RCC. Of those, 164 were PD-L1-positive. Participants were randomly assigned to receive intravenous atezolizumab plus bevacizumab, atezolizumab alone, or oral sunitinib alone until disease progression or unacceptable toxicity.

Among patients whose tumors expressed PD-L1, those treated with dual immunotherapy had a 36% reduction in the risk of disease progression or death compared with sunitinib alone (hazard ratio [HR], 0.64; 95% CI, 0.38-1.08; P = .095); median progression-free survival was 14.7 months vs 7.8 months, respectively.

Investigators observed no progression-free survival advantage with atezolizumab plus bevacizumab compared with sunitinib alone in the overall population (HR, 1.00; 95% CI, 0.69-1.45). Median follow-up was 20.7 months and median duration of response has not yet been reached.

There was also no significant difference in progression-free survival between patients treated with atezolizumab alone and those who received sunitinib in the total population and in the PD-L1-positive subgroup.

In the overall population, confirmed objective response rates were 32% (95% CI, 23-42), 25% (95% CI, 17-35), and 29% (95% CI, 20-39) in the atezolizumab plus bevacizumab, atezolizumab alone, and sunitinib arms, respectively; among those with PD-L1-expressing tumors, 46%, 28%, and 27% achieved objective responses, respectively.

Researchers observed treatment-related grade 3 to 4 adverse events in 40%, 16%, and 57% of patients in the atezolizumab plus bevacizumab, atezolizumab, and sunitinib groups, respectively; 3%, 2%, and 2%, respectively, died due to adverse events.

RELATED: Impact of Early Immunotherapy Discontinuation in mRCC

The ongoing phase 3 IMmotion151 study (ClinicalTrials.gov Identifier: NCT02420821) is recruiting participants to evaluate atezolizumab combined with bevacizumab vs sunitinib alone in the same population.

Reference

  1. McDermott DF, Atkins MB, Motzer RJ, et al. A phase II study of atezolizumab (atezo) with or without bevacizumab (bev) versus sunitinib (sun) in untreated metastatic renal cell carcinoma (mRCC) patients (pts). Paper presented at: 2017 Genitourinary Cancers Symposium; February 16-18, 2017; Orlando, FL.

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