Efficacy and correlative analyses of avelumab plus axitinib versus sunitinib in sarcomatoid renal cell carcinoma: post hoc analysis of a randomized clinical trial

Choueiri, T. K. et al. (2021) Efficacy and correlative analyses of avelumab plus axitinib versus sunitinib in sarcomatoid renal cell carcinoma: post hoc analysis of a randomized clinical trial. ESMO Open, 6(3), 100101. (doi: 10.1016/j.esmoop.2021.100101) (PMID:33901870) (PMCID:PMC8099757)

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

• Item Type: Articles
• Additional Information: This work was sponsored by Pfizer as part of an alliance between Pfizer and Merck KGaA, Darmstadt, Germany. The conduct of the trial at the Memorial Sloan Kettering Cancer Center was supported in part by Memorial Sloan Kettering Cancer Center Support Grant/Core Grant [grant number P30 CA008748]. Medical writing assistance was provided by Amy Davidson of ClinicalThinking and funded by Pfizer and Merck KGaA, Darmstadt, Germany.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Venugopal, Dr Balaji
• Authors: Choueiri, T. K., Larkin, J., Pal, S., Motzer, R. J., Rini, B. I., Venugopal, B., Alekseev, B., Miyake, H., Gravis, G., Bilen, M. A., Hariharan, S., Chudnovsky, A., Ching, K. A., Mu, X. J., Mariani, M., Robbins, P. B., Huang, B., di Pietro, A., and Albiges, L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: ESMO Open
• Publisher: Elsevier
• ISSN: 2059-7029
• ISSN (Online): 2059-7029
• Published Online: 23 April 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in ESMO Open 6(3): 100101
• Publisher Policy: Reproduced under a Creative Commons licence