UPFRONT IMMUNOTHERAPY FOR RENA CANCER

In a phase 3 study of patients with previously untreated metastatic renal cell cancer (mRCC), use of the anti-PD-L1 immune checkpoint inhibitor atezolizumab (Tecentriq, Roche) in combination with bevacizumab (Avastin, Roche) delayed disease progression by about 3 months longer than standard treatment with sunitinib (Sutent, Pfizer), with fewer side effects.

The benefit of atezolizumab plus bevacizumab was greater for patients with programmed cell death ligand 1 (PD-L1)–positive tumors.

Results of the study "support the consideration of atezolizumab plus bevacizumab as a first-line treatment option" in patients with PD-L1–positive mRCC, said lead author, Robert J. Motzer, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, New York City.

He discussed the results at a presscast February 5 ahead of the Genitourinary Cancers Symposium (GUCS) 2018, which will be held later this week in San Francisco, California.

The study, known as IMmotion151, is the first randomized, phase 3 trial of a PD-L1/programmed cell death 1 pathway inhibitor (atezolizumab) combined with an anti–vascular endothelial growth factor agent (bevacizumab) as first-line therapy in patients with previously untreated mRCC.

A total of 915 patients were randomly assigned to receive atezolizumab (1200 mg) plus bevacizumab (15 mg/kg) intravenously every 3 weeks or oral sunitinib (50 mg/day for 4 weeks, followed by 2 weeks off treatment).  Patients were stratified by PD-L1 status (<1 362="" a="" cells="" expression="" immune="" of="" on="" p="" patients="" pd-l1="" positive.="" total="" tumor-infiltrating="" vs="" were="">

At a median follow-up of 15 months, PD-L1–positive patients treated with atezolizumab plus bevacizumab had a 26% lower chance of disease progression than those treated with sunitinib. The median time to progression was 3.5 months longer with the combined treatment than with sunitinib. The overall response rate (ORR) was also better with atezolizumab plus bevacizumab.

Table 1. Results in PD-L1–Positive Patients

Outcome	Atezolizumab + Bevacizumab (n = 178)	Sunitinib (n = 184)	Hazard Ratio
Median PFS	11.2 mo (8.9 - 15.0 mo)	7.7 mo (6.8 - 9.7 mo)	0.74 (0.57 - 0.96)
ORR (%)	43 (35 - 50)	35 (28 - 42)
Values in parentheses are 95% confidence intervals. ORR, objective response rate; PFS, progression-free survival.

The benefits of atezolizumab plus bevacizumab were also observed, though more modest, in the entire study population (intention-to-treat [ITT] population), Dr Motzer reported. Patients who received atezolizumab and bevacizumab had a 17% lower chance of progression, with a median time of 2.4 months longer until the cancer worsened.

Table 2. Results in ITT Population 

Outcome	Atezolizumab + Bevacizumab (n = 454)	Sunitinib (n = 461)	Hazard Ratio
Median PFS	11.2 mo (9.6 - 13.3 mo)	8.4 mo (7.5 - 9.7 mo)	0.83 (0.70 - 0.97)
ORR (%)	37 (32 - 41)	33 (29 - 38)
Values in parentheses are 95% confidence intervals. ORR, objective response rate; PFS, progression-free survival.

"The results of the overall survival in the group of patients expressing PD-L1 and in the ITT group are immature. They await further follow-up but certainly the trend that we are seeing, or the path that is being taken here, is in favor of atezolizumab plus bevacizumab over sunitinib," said Dr Motzer.

"One of the main benefits of the atezolizumab plus bevacizumab is its safety profile," Dr Motzer said. "It is very well tolerated" and compared with sunitinib, was associated with fewer high-grade treatment-related adverse events (40% vs 54%), low steroid use, and delayed symptom interference with daily life, he noted.

[This study represents an] important breakthrough in kidney cancer therapy. Dr Sumanta Pal

Briefing moderator and American Society of Clinical Oncology expert Sumanta Pal, MD, said this study represents an "important breakthrough in kidney cancer therapy."

"For several years now, we've had debates on which treatment strategy is best for this disease — targeted therapy or immune therapy.  This study, which is really the first of its kind, points to a combination of both as being highly effective in delaying cancer growth, and there is also an early trend toward improving survival. Another important piece of this data is the tolerability of combining targeted therapy with immune therapy," said Dr Pal, a medical oncologist at the City of Hope Cancer Center in Los Angeles, California.

Dr Pal also said he agrees with Dr Motzer that the data support consideration of bevacizumab and atezolizumab as a first-line option.

This study was funded by F. Hoffmann-La Roche Ltd. Dr Motzer and several study authors have financial ties to industry, including Pfizer, Bristol-Myers Squibb and Genentech/Roche. Dr Pal has financial ties to multiple pharmaceutical companies.

Genitourinary Cancers Symposium (GUCS) 2018. Abstract 578. To be presented February 8, 2018.