Data on the effects of prior cytoreductive nephrectomy (CN) in patients with renal cell carcinoma (RCC) with synchronous metastases (M1 disease) before immune checkpoint inhibitor (ICI) treatment are limited. In this post hoc analysis of treatment-naive patients with advanced RCC from the phase 3 JAVELIN Renal 101 trial, we assessed efficacy outcomes in the avelumab + axitinib and sunitinib arms in patients who were initially diagnosed with M1 disease (n = 412) grouped by prior CN (yes vs no). Progression-free survival (PFS) and overall survival (OS) were analyzed using multivariable Cox regression, and objective response rates (ORRs) were analyzed using logistic regression. After adjusting for imbalances in baseline variables, the hazard ratio (HR) for PFS in the prior CN versus no prior CN subgroup was 0.79 (95% confidence interval [CI] 0.53-1.16) in the avelumab + axitinib arm, and 1.15 (95% CI 0.77-1.70) in the sunitinib arm. The corresponding HRs for OS were 0.59 (95% CI 0.38-0.93) and 0.86 (95% CI, 0.55-1.34), and the odds ratios for ORR were 2.67 (95% CI 1.32-5.41) and 2.02 (95% CI 0.82-4.94), respectively. Prospective studies of the potential benefits of CN and its appropriate timing in patients receiving first-line treatment with ICI-containing combinations are warranted. PATIENT SUMMARY: This study looked at patients with kidney cancer whose disease had already spread outside the kidneys when it was first detected. We found that patients whose kidney had been removed before starting treatment with avelumab + axitinib had better outcomes than those whose kidney had not been removed. For patients treated with sunitinib, the results were more similar between the groups with and without prior kidney removal. However, statistical tests did not find any significant differences. The JAVELIN Renal 101 trial is registered on ClinicalTrials.gov as NCT02684006.
European urology. 2023 Oct 16 [Epub ahead of print]
Marc-Oliver Grimm, Mototsugu Oya, Toni K Choueiri, Robert M Motzer, Manuela Schmidinger, David I Quinn, Gwenaelle Gravis-Mescam, Elena Verzoni, Alfonsus J M Van den Eertwegh, Alessandra di Pietro, Mariangela Mariani, Jing Wang, Despina Thomaidou, Laurence Albiges
Jena University Hospital, Jena, Germany. Electronic address: ., Keio University School of Medicine, Tokyo, Japan., Dana-Farber Cancer Institute, Boston, MA, USA., Memorial Sloan Kettering Cancer Center, New York, NY, USA., Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA., Institut Paoli-Calmettes, Aix-Marseille University, INSERM, CNRS, CRCM, Marseille, France., Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy., Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands., Pfizer SRL, Milan, Italy., Pfizer, Cambridge, MA, USA., Pfizer, Athens, Greece., Gustave Roussy Cancer Campus, University of Paris Saclay, Villejuif, France.