Adjuvant therapy with the anti–PD-L1 therapy atezolizumab failed to improve disease-free survival compared to placebo in patients with renal cell carcinoma (RCC) at high risk of recurrence after resection, according to results of the phase III IMmotion010 trial presented by Axel Bex, MD, PhD, at the European Society for Medical Oncology (ESMO) Congress 2022 (Abstract LBA66). The study was also published in The Lancet to coincide with Dr. Bex’s presentation.
At a median follow-up of 44.7 months, the median investigator-assessed disease-free survival was 57.2 months in patients who received atezolizumab compared to 49.5 months in the placebo group. At 2 years, the rates of disease-free survival were 67% for atezolizumab vs 65% for placebo.
“There was no evidence that atezolizumab reduced the risk of recurrence vs placebo... [and] no evidence of reduction in the risk of death with atezolizumab,”— Axel Bex, MD, PhD
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“There was no evidence that atezolizumab reduced the risk of recurrence vs placebo,” and there was “no evidence of reduction in the risk of death with atezolizumab,” said Dr. Bex, of Royal Free London NHS Foundation Trust and UCL Division of Surgery and Interventional Science, Netherlands/UK.
These results were somewhat of a surprise, since the KEYNOTE-564 trial showed that adjuvant immunotherapy with pembrolizumab led to a 32% reduction in risk of disease or death compared with placebo, resulting in approval by the U.S. Food and Drug Administration for pembrolizumab in this setting.
IMmotion010 was a randomized, double-blind, phase III trial conducted at 215 clinical sites in 28 countries. Starting in 2017, 778 patients were enrolled with clear cell RCC or sarcomatoid component who were at increased risk of recurrence following nephrectomy with or without metastasectomy.
At baseline, median age was 60 years, 73% of patients were male, and about 80% were White. Overall, 79% of patients had an Eastern Cooperative Oncology Group performance status of 0 and 21% had an ECOG performance status of 1. Sixty-four percent of patients had stage T2 or T3a disease, and 22% had stage T3b–c or T4 or N+ disease. Forty percent of patients had PD-L1–negative tumors and 60% had PD-L1–positive tumors.
Patients were randomly assigned in a 1:1 ratio to receive adjuvant therapy with atezolizumab at 1,200 mg (n = 390) once every 3 weeks for 16 cycles or 1 year or matching placebo (n = 388). The primary endpoint was investigator-assessed disease-free survival in the intention-to-treat population.
Atezolizumab was well tolerated, and safety results were consistent with the known safety profile of atezolizumab. The most frequently reported grade 3 or 4 adverse events were hypertension (2% in the atezolizumab arm vs 4% in the placebo arm), hyperglycemia (3% vs 2%, respectively), and diarrhea (1% vs 2%, respectively). Serious adverse events were reported in 18% (n = 69) of the atezolizumab arm and 12% (n = 46) of the placebo arm. No treatment-related deaths were reported.
Given the discordant results of studies of adjuvant immunotherapy with checkpoint inhibitors, some of them presented at this meeting, further studies are needed to clarify the role of adjuvant immunotherapy in RCC.