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

• Type of Material: Article
• Authors: TK Choueiri, Dana-Farber Cancer Institute; J Larkin, The Royal Marsden NHS Foundation Trust; S Pal, City of Hope Comprehensive Cancer Center; RJ Motzer, Memorial Sloan Kettering Cancer Center; B Rini, Vanderbilt University; B Venugopal, University of Glasgow; B Alekseev, P. Hertsen Moscow Oncology Research Institute; H Miyake, Hamamatsu University; G Gravis, Aix-Marseille Université; Mehmet Bilen, Emory University; S Hariharan, Pfizer; A Chudnovsky, Pfizer; KA Ching, Pfizer; XJ Mu, Pfizer; M Mariani, Pfizer; PB Robbins, Pfizer; B Huang, Pfizer; A di Pietro, Pfizer; L Albiges, Institut Gustave Roussy
• Language: English
• Date: 2021-04-23
• Publisher: ELSEVIER
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Authors
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.esmoop.2021.100101
• Title of Journal or Parent Work: ESMO OPEN
• Volume: 6
• Issue: 3
• Start Page: 100101
• End Page: 100101
• Grant/Funding 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.
• Keywords: IMMUNE CELLS; JAVELIN Renal 101; axitinib; BREAST; sarcomatoid; Life Sciences & Biomedicine; SELECTION; TARGETED THERAPY; 1ST-LINE; GENE SIGNATURE; RECEPTOR; renal cell carcinoma; Science & Technology; MELANOMA; avelumab; RESISTANCE; Oncology; EXPRESSION
• Research Categories: Health Sciences, Oncology

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.