Among patients with advanced renal cell carcinoma (RCC), those with sarcomatoid histology (sRCC) have the poorest prognosis. This analysis assessed the efficacy of avelumab plus axitinib versus sunitinib in patients with treatment-naive advanced sRCC.
The randomized, open-label, multicenter, phase III JAVELIN Renal 101 trial (NCT02684006) enrolled patients with treatment-naive advanced RCC. Patients were randomized 1 : 1 to receive either avelumab plus axitinib or sunitinib following standard doses and schedules. Assessments in this post hoc analysis of patients with sRCC included efficacy (including progression-free survival) and biomarker analyses.
A total of 108 patients had sarcomatoid histology and were included in this post hoc analysis; 47 patients in the avelumab plus axitinib arm and 61 in the sunitinib arm. Patients in the avelumab plus axitinib arm had improved progression-free survival [stratified hazard ratio, 0.57 (95% confidence interval, 0.325-1.003)] and a higher objective response rate (46.8% versus 21.3%; complete response in 4.3% versus 0%) versus those in the sunitinib arm. Correlative gene expression analyses of patients with sRCC showed enrichment of gene pathway scores for cancer-associated fibroblasts and regulatory T cells, CD274 and CD8A expression, and tumors with The Cancer Genome Atlas m3 classification.
In this subgroup analysis of JAVELIN Renal 101, patients with sRCC in the avelumab plus axitinib arm had improved efficacy outcomes versus those in the sunitinib arm. Correlative analyses provide insight into this subtype of RCC and suggest that avelumab plus axitinib may increase the chance of overcoming the aggressive features of sRCC.
ESMO open. 2021 Apr 23 [Epub ahead of print]
T K Choueiri, J Larkin, S Pal, R J Motzer, B I Rini, B Venugopal, B Alekseev, H Miyake, G Gravis, M A Bilen, S Hariharan, A Chudnovsky, K A Ching, X J Mu, M Mariani, P B Robbins, B Huang, A di Pietro, L Albiges
Department of Medical Oncology, The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, USA. Electronic address: ., Renal and Skin Units, The Royal Marsden NHS Foundation Trust, Chelsea, London, UK., Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, USA., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA., Department of Medicine, Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, USA., Institute of Cancer Sciences, University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, Scotland, UK., P. Hertsen Moscow Oncology Research Institute, Moscow, Russia., Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan., Department of Medical Oncology, Institut Paoli-Calmettes, Aix-Marseille Université, Inserm, CNRS, CRCM, Marseille, France., Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, USA., Oncology, Pfizer, New York, USA., Oncology, Pfizer, Cambridge, USA., Computational Biology, Pfizer, San Diego, USA., Immuno-Oncology, Pfizer, Milan, Lombardia, Italy., Translational Oncology, Pfizer, San Diego, USA., Biostatistics, Pfizer, Groton, USA., Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.