Combination of Tecentriq, Avastin Aids Kidney Cancer PFS

Patients with high PD-L1 level show benefit in first-line treatment

The combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) improved progression-free survival compared with sunitinib (Sutent, Pfizer) as initial treatment for patients whose advanced kidney disease expressed programmed death-ligand 1 (PD-L1) in the phase 3 IMmotion151 trial, Genentech has announced.

The IMmotion151 study met its co-primary endpoint of investigator-assessed progression-free survival (PFS), demonstrating that the combination of atezolizumab and bevacizumab (both made by Genentech) provided a statistically significant and clinically meaningful reduction in PFS in people whose disease had PD-L1 expression of at least 1% compared with sunitinib for the first-line treatment of people who have advanced or metastatic renal cell carcinoma (mRCC).

Observations of a pre-specified subgroup analysis of the atezolizumab/bevacizumab combination indicated that, in people whose disease expressed PD-L1, a numerical difference favoring atezolizumab was seen across all patient risk factor groups (favorable, intermediate, and poor) compared to sunitinib. However, due to the study design these data could not be assessed for statistical significance and are descriptive only. Assessment of secondary endpoints is ongoing.

Safety for the atezolizumab/bevacizumab combination appeared consistent with the known safety profile of the individual medicines and what was previously reported in the phase 2 IMmotion150 study. No new safety signals were identified with the combination.

Results will be presented at an upcoming oncology conference in 2018. Top-line results from the co-primary endpoint of overall survival (OS) are not mature.

“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, Genentech’s chief medical officer and head of Global Product Development. “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 the second successive positive phase 3 study of atezolizumab that includes a bevacizumab combination component as an initial treatment. This follows the positive phase 3 non-squamous non–small-cell lung cancer IMpower150 study that showed the combination of atezolizumab, bevacizumab, and chemotherapy demonstrated a PFS advantage over bevacizumab plus chemotherapy.

IMmotion151 is a multicenter, randomized, open-label study to evaluate the efficacy and safety of atezolizumab and bevacizumab versus sunitinib in people with inoperable, locally advanced, or metastatic renal cell carcinoma (RCC) who have not received prior systemic active or experimental therapy. It enrolled 915 people globally who were randomized 1:1 to receive atezolizumab and bevacizumab, or sunitinib alone.

People in the atezolizumab and bevacizumab arm received atezolizumab at a fixed dose of 1,200 mg and bevacizumab at a dose of 15 mg/kg via intravenous infusion every three weeks until loss of clinical benefit or unacceptable toxicity. People in the sunitinib arm received sunitinib 50 mg orally, once daily for four weeks followed by two weeks rest until loss of clinical benefit or unacceptable toxicity.

According to the American Cancer Society, more than 63,000 people will be diagnosed with kidney cancer in 2017. Renal cell carcinoma accounts for approximately 90% of all cases.

Atezolizumab is a monoclonal antibody designed to bind with PD-L1 on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, atezolizumab may enable the re-activation of T cells. Bevacizumab is a biologic antibody designed to specifically bind to the protein vascular endothelial growth factor, which plays an important role throughout the lifecycle of the tumor to develop and maintain blood vessels. Bevacizumab is designed to interfere with the tumor blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells.

Source: Genentech; December 11, 2017.