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Atezolizumab plus bevacizumab extends PFS in metastatic renal cell carcinoma
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The combination of atezolizumab and bevacizumab conferred longer PFS than sunitinib as first-line treatment for metastatic renal cell carcinoma, according to results of the phase 3 IMmotion151 clinical trial scheduled for presentation at the Genitourinary Cancers Symposium.
The benefit appeared pronounced among patients with PD-L1-positive tumors.
“Kidney cancer occurs in 62,000 people each year in the U.S.,” Robert J. Motzer, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, said during a press cast. “The mainstay of treatment is sunitinib, [or] bevacizumab and interferon, but there has been a lot of interesting excitement around checkpoint inhibitors in this disease — in particular with combinations, including atezolizumab plus bevacizumab.”
As HemOnc Today previously reported, results from the phase 2 IMmotion150 trial showed longer investigator-assessed PFS in the intention-to-treat population with atezolizumab (Tecentriq, Genentech), an anti-PD-L1 therapy, and bevacizumab (Avastin, Genentech), an anti-VEGF therapy, than with sunitinib (Sutent, Pfizer; 11 months vs. 7.8 months).
IMmotion151 was the first randomized phase 3 study of PD-1/PD-L1-directed therapy and VEGF pathway inhibition in the first-line setting of metastatic renal cell carcinoma.
The trial included 915 patients with treatment-naive locally advanced or metastatic renal cell carcinoma from various sites worldwide.
Researchers randomly assigned patients to 1,200 mg IV atezolizumab plus 15 mg/kg bevacizumab every 3 weeks, or 50 mg sunitinib orally in a conventional 4-weeks-on, 2-weeks-off schedule.
Independent review facility-assessed PFS among patients with PD-L1-positive tumors (n = 362) and OS in the intention-to-treat population served as co-primary endpoints. Secondary endpoints included PFS in the intention-to-treat population (n = 915), duration of response and objective response rate.
The median follow-up for survival was 15 months.
The combination regimen conferred longer median PFS among patients with PD-L1-positive tumors (11.2 months vs. 7.7 months; HR = 0.74; 95% CI, 0.57-0.96) and among intention-to-treat patients (11.2 months vs. 8.4 months; HR = 0.83; 95% CI, 0.7-0.97) compared with sunitinib.
“[These numbers] met the predetermined boundary of significance,” Motzer said.
PFS benefit remained comparable across analyzed subgroups, including those based on Memorial Sloan Kettering Cancer Center risk score, liver metastases and sarcomatoid histology.
OS data was premature at the time of the first interim analysis, Motzer said.
“We await further follow-up but, certainly, the trend we are seeing ... is in favor of atezolizumab and bevacizumab,” Motzer said.
Among patients with PD-L1 positive tumors, the ORR was 43% with the combination vs. 35% with sunitinib. Median duration of response was not estimable (95% CI, 12.4-not reached) for the combination and 12.9 months (95% CI, 9.8-not reached) for sunitinib.
Treatment-related grade 3 to grade 4 adverse events appeared lower with the combination regimen than with sunitinib (40% vs. 54%).
One adverse event commonly observed was leaking protein, which is associated with bevacizumab treatment, Motzer said.
Treatment-related all-grade adverse events led to treatment discontinuation among 12% of the atezolizumab-bevacizumab group and 8% of the sunitinib group.
“These study results support the consideration of atezolizumab plus bevacizumab as a first-line treatment option for PD-L1-positive patients with advanced renal cell carcinoma,” Motzer said. – by Melinda Stevens
Reference:
Motzer RJ, et al. Abstract 578. Scheduled for presentation at: Genitourinary Cancers Symposium; Feb. 8-10, 2018; San Francisco.
Disclosures: Motzer reports consultant/advisory roles with or research funding to his institution from Bristol-Myers Squibb, Eisai, Exelixis, Genentech/Roche, GlaxoSmithKline Merck, Novartis and Pfizer. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Sumanta K. Pal, MD
The study represents an important breakthrough in kidney cancer therapy. For several years, we’ve hosted debates on which treatment strategy is best for this disease: targeted therapy or immunotherapy. This study — which is the first of its kind — points to a combination of both as being highly effective in delaying tumor growth, with also an early trend toward improving survival.
The higher rate of complete response with bevacizumab and atezolizumab was very encouraging. Achieving total eradication of metastatic disease is the highest bar we can strive for in this setting.
Another important piece of these data is the tolerability of combining targeted therapy and immunotherapy with atezolizumab and bevacizumab. The side effect profile in several respects seems to be superior to traditional oral-targeted drugs, such as sunitinib, used in this setting. In my opinion, the side effect profile also compares favorably to what we’ve seen to date for a dual immunotherapy regimen, mainly nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb). That regimen also demonstrated improved outcomes relative to sunitinib among patients with newly diagnosed metastatic kidney cancer, but nearly 60% of patients required steroids in that study for management of side effects compared with the 16% reported in this trial.
I would agree these data support consideration of atezolizumab and bevacizumab as a first-line option. Many may be curious about implications of the biomarkers assessed in this study, mainly PD-L1. Researchers assessed PD-L1 — the target of atezolizumab — in tissues of patients enrolled in the study. I was intrigued to see there was benefit with a combination of bevacizumab and atezolizumab irrespective of presence or absence of PD-L1.
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