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.

The standard of care for locoregional renal cell carcinoma is surgery, but many patients experience recurrence. The objective of the current study was to determine if adjuvant atezolizumab (vs placebo) delayed recurrence in patients with an increased risk of recurrence after resection.

IMmotion010 is a randomised, double-blind, multicentre, phase 3 trial conducted in 215 centres in 28 countries. Eligible patients were patients aged 18 years or older with renal cell carcinoma with a clear cell or sarcomatoid component and increased risk of recurrence. After nephrectomy with or without metastasectomy, patients were randomly assigned (1:1) to receive atezolizumab (1200 mg) or placebo (both intravenous) once every 3 weeks for 16 cycles or 1 year. Randomisation was done with an interactive voice-web response system. Stratification factors were disease stage (T2 or T3a vs T3b-c or T4 or N+ vs M1 no evidence of disease), geographical region (north America [excluding Mexico] vs rest of the world), and PD-L1 status on tumour-infiltrating immune cells (<1% vs ≥1% expression). The primary endpoint was investigator-assessed disease-free survival in the intention-to-treat population, defined as all patients who were randomised, regardless of whether study treatment was received. The safety-evaluable population included all patients randomly assigned to treatment who received any amount of study drug (ie, atezolizumab or placebo), regardless of whether a full or partial dose was received. This trial is registered with, NCT03024996, and is closed to further accrual.

Between Jan 3, 2017, and Feb 15, 2019, 778 patients were enrolled; 390 (50%) were assigned to the atezolizumab group and 388 (50%) to the placebo group. At data cutoff (May 3, 2022), the median follow-up duration was 44·7 months (IQR 39·1-51·0). Median investigator-assessed disease-free survival was 57·2 months (95% CI 44·6 to not evaluable) with atezolizumab and 49·5 months (47·4 to not evaluable) with placebo (hazard ratio 0·93, 95% CI 0·75-1·15, p=0·50). The most common grade 3-4 adverse events were hypertension (seven [2%] patients who received atezolizumab vs 15 [4%] patients who received placebo), hyperglycaemia (ten [3%] vs six [2%]), and diarrhoea (two [1%] vs seven [2%]). 69 (18%) patients who received atezolizumab and 46 (12%) patients who received placebo had a serious adverse event. There were no treatment-related deaths.

Atezolizumab as adjuvant therapy after resection for patients with renal cell carcinoma with increased risk of recurrence showed no evidence of improved clinical outcomes versus placebo. These study results do not support adjuvant atezolizumab for treatment of renal cell carcinoma.

F Hoffmann-La Roche and Genentech, a member of the Roche group.

Lancet (London, England). 2022 Sep 09 [Epub ahead of print]

Sumanta Kumar Pal, Robert Uzzo, Jose Antonio Karam, Viraj A Master, Frede Donskov, Cristina Suarez, Laurence Albiges, Brian Rini, Yoshihiko Tomita, Ariel Galapo Kann, Giuseppe Procopio, Francesco Massari, Matthew Zibelman, Igor Antonyan, Mahrukh Huseni, Debasmita Basu, Bo Ci, William Leung, Omara Khan, Sarita Dubey, Axel Bex

Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. Electronic address: ., Department of Urology, Fox Chase Cancer Center, Philadelphia, PA, USA., Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Urology and Winship Cancer Institute, Emory University, Atlanta, GA, USA., Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; University Hospital of Southern Denmark, Esbjerg, Denmark., Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain., Department of Cancer Medicine, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA., Department of Urology, Niigita University Medical and Dental Hospital, Niigata University, Niigata, Japan., Hospital Alemão Oswaldo Cruz, São Paulo, Brazil., Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy., Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA., V.I. Shapoval Regional Medical Clinical Center of Urology and Nephrology, Kharkiv, Ukraine., Genentech, South San Francisco, CA, USA., Roche Product, Welwyn Garden City, UK., Department of Urology, The Royal Free London NHS Foundation Trust, University College London Division of Surgery and Interventional Science, London, UK; The Netherlands Cancer Institute, Amsterdam, Netherlands.