The double-blind phase 3 IMmotion010 trial randomized patients with resected renal cell carcinoma at increased risk of recurrence to adjuvant atezolizumab or placebo.
Axel Bex, MD, PhD
Atezolizumab (Tecentriq) did not improve clinical outcomes vs placebo when used as adjuvant therapy post-resection in patients with renal cell carcinoma (RCC) at increased risk of recurrence, according to findings from the phase 3 IMmotion010 trial presented at the 2022 ESMO Congress.1,2
At a median follow-up of 44.7 months (IQR, 39.1-51.0), the median investigator-assessed disease-free survival (DFS) was 57.2 months (95% CI, 44.6 – not evaluable) with atezolizumab compared to 49.5 months (47.4 – not evaluable) with placebo (HR, 0.93; 95% CI, 0.75-1.15; P = 0.50). The 2-year DFS rates were 67% vs 65%, respectively.
“There was no evidence that atezolizumab reduced the risk of recurrence versus placebo,” said first author Axel Bex, MD, PhD, Royal Free London NHS Foundation Trust and UCL Division of Surgery and Interventional Science, Netherlands/UK, adding that there was also “no evidence of reduction in the risk of death with atezolizumab.”
The double-blind phase 3 IMmotion010 trial (NCT03024996) enrolled 778 patients with RCC at 215 clinical sites across 28 countries between January 3, 2017, and February 15, 2019. Patients had disease with a clear cell or sarcomatoid component and increased risk of recurrence following nephrectomy with or without metastasectomy.
The median patient age was 60 years, 73% of patients were male, and about 80% of patients were White. Overall, 79% of patients had an ECOG performance status (PS) of 0 and 21% had an ECOG PS of 1. Sixty-four percent of patients had stage T2 or T3a disease, and 22% of patients had stage T3b–c or T4 or N+ disease. Forty percent of patients were negative for PD-L1 immune cell expression on their tumors and 60% were positive.
Patients were randomized in a 1:1 ratio to adjuvant atezolizumab (390 patients) placebo (388 patients). Atezolizumab (1200 mg) or matching placebo were both administered intravenously once every 3 weeks for 16 cycles or 1 year. Investigator-assessed DFS in the intention-to-treat (ITT) population was the primary end point.
Regarding safety, Bex said, “Atezolizumab was well tolerated, and safety results were consistent with the known safety profile of atezolizumab.”
The most frequently reported grade 3/4 adverse events (AEs) 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 AEs occurred in 18% (69 patients) of the atezolizumab arm and 12% (46 patients) of the placebo arm. There were no patient deaths that were related to study treatment.
The study results for the trial were inconsistent with previously published data from the KEYNOTE-564 trial showing improved outcomes with adjuvant immunotherapy in patients with fully resected RCC. Specifically, the study showed that pembrolizumab (Keytruda) induced a 32% reduction in the risk of disease recurrence or death compared with placebo (HR, 0.68; P = .0010),3 leading to the FDA approval and European approval of the immunotherapy in this setting.
Given the contrasting outcomes with immune checkpoint inhibitors, Bex said in his concluding remarks that, “Further studies are needed to clarify the role of immunotherapy in the adjuvant setting for RCC.”
1. Bex A, Uzzo R, Karam JA, et al. IMmotion010: Efficacy and safety from the phase III study of atezolizumab (atezo) vs placebo (pbo) as adjuvant therapy in patients with renal cell carcinoma (RCC) at increased risk of recurrence after resection. Ann Oncol. 2022;33(suppl 7):S808-S869. doi:10.1016/annonc/annonc1089
2. Kumar Pal SK, Uzzo R, Karam JA, et al. Adjuvant atezolizumab versus placebo for patients with renal cell carcinoma at increased risk of recurrence following resection (IMmotion010): a multicentre, randomised, double-blind, phase 3 trial [published online September 10, 2022]. Lancet. doi:10.1016/S0140-6736(22)01658-0
3. FDA approves pembrolizumab for adjuvant treatment of renal cell carcinoma. Published online November 17, 2021. Accessed November 17, 2021. https://bit.ly/3cmJeXs