Atezolizumab Plus Bevacizumab Meets Primary Endpoint for PFS in Advanced or Metastatic mRCC

In top-line results from the phase III IMmotion151 trial, the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) was associated with a statistically significant reduction in the risk for death or progression in patients with PD-L1

Sandra Horning, MD

In top-line results from the phase III IMmotion151 trial, the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) was associated with a statistically significant reduction in the risk for death or progression in patients with PD-L1—positive advanced or metastatic renal cell carcinoma (mRCC).

Genentech, the developer of both agents, stated in a news release that the co-blockade of VEGF with bevacizumab and PD-L1 with atezolizumab met the co-primary endpoint for investigator-assessed progression-free survival (PFS).

“We are encouraged by these results as they add to the emerging body of evidence that supports our rationale for this combination. We believe that the regimen of Tecentriq and Avastin may enhance the potential of the immune system in the initial treatment of advanced kidney cancer,” said Sandra Horning, MD, chief medical officer and head of global product development of Genentech. “We will discuss these data with health authorities globally and hope to bring this combination forward as a potential new treatment option as soon as possible.”

IMmotion151 is a global, multicenter, randomized, open-label trial evaluating the efficacy and safety of atezolizumab and bevacizumab versus sunitinib (Sutent) for patients who have not received prior systemic active or experimental therapy.

Patients were randomly assigned to 1200 mg of atezolizumab and 15 mg/kg bevacizumab intravenously every 3 weeks until loss of clinical benefit or unacceptable toxicity. Patients in the control arm received 50 mg of oral sunitinib once daily for 4 weeks followed by 2 weeks rest until loss of clinical benefit or unacceptable toxicity. The co-primary endpoints were PFS in patients whose tumors expressed PD-L1 ≥1% and overall survival in the intent-to-treat population.

The company did not release any data from the trial, stating that Initial results will be presented at a medical conference next year. Top-line results for OS are not mature.

Results from phase II IMmotion 150 trial were presented in September at the 2017 ESMO Congress. In that study, treatment-naïve patients with mRCC were randomly assigned to 50 mg oral sunitinib daily in a 4-week on, 2-week off cycle (n = 101), 1200 mg atezolizumab monotherapy every 3 weeks (n = 103), or 1200 mg atezolizumab plus 15 mg/kg bevacizumab (n = 101) administered every 3 weeks. Treatment beyond progression was allowed in the atezolizumab arms, but not the sunitinib arm. Crossover upon progression was allowed for non-European patients.

At a median follow-up of 25.7 months, the median PFS by RECIST criteria was 7.8 months with sunitinib versus 5.5 months with atezolizumab monotherapy (HR, 1.13; P = 0.45) and 11.0 months with the combination (HR, 0.88; P = .44). By immune-modified RECIST (imRECIST) criteria, median PFS was 9.9 months with sunitinib versus 8.5 months with atezolizumab monotherapy (HR, 1.05; P = .77), and 17.3 months with atezolizumab and bevacizumab (HR, 0.78; P = .16).

PFS event-free rates at 6 months were 56.4% versus 66.4% with sunitinib, 45.6% versus 63.3% with atezolizumab, and 63.2% versus 75.0% with atezolizumab and bevacizumab treatment in the overall and imRECIST populations, respectively.

The investigator-assessed overall response rate (ORR) was 32% with sunitinib, 24.3% with atezolizumab monotherapy, and 34.7% with the atezolizumab/bevacizumab combination in the overall population versus 28.3%, 27.8%, and 48.0%, respectively, in the PD-L1—positive population. The rates of complete response, partial response, and stable disease were similar, but lower in the overall population compared with the PD-L1–positive cohort.

Both the combination and atezolizumab alone were better tolerated than sunitinib. Twelve percent of patients in the sunitinib arm experienced treatment-related serious adverse events (AEs) compared with 14.6% for atezolizumab alone and 23.8% for atezolizumab plus bevacizumab.

Patients assigned to the combination were more likely to withdraw due to AEs (21.8%) compared with 13.0% for sunitinib and 6.8% for atezolizumab monotherapy. However, patients assigned to sunitinib were more likely to require dose modification or interruption due to AEs (70.0%) than those assigned to monotherapy (27.2%) or the combination (61.4%).

Two (2%) patients in the sunitinib arm and 1 (1%) patient assigned to the combination died due to an AE.

Powles T, McDermotee SF, Rini B, et al. IMmotion150: Novel radiological endpoints and updated data from a randomized phase II trial investigating atezolizumab (atezo) with or without bevacizumab (bev) vs sunitinib (sun) in untreated metastatic renal cell carcinoma (mRCC). In: Proceedings from the 2017 ESMO Congress; September 8-12, 2017; Madrid, Spain. Abstract LBA39.