Immune Checkpoint Therapy Combinations in Adult Advanced MiT Family Translocation Renal Cell Carcinomas

• Published in: The oncologist (Dayton, Ohio) Ohio), 2023-05, Vol.28 (5), p.433-439
• Main Authors: Alhalabi, Omar, Thouvenin, Jonathan, Négrier, Sylvie, Vano, Yann-Alexandre, Campedel, Luca, Hasanov, Elshad, Bakouny, Ziad, Hahn, Andrew W, Bilen, Mehmet Asim, Msaouel, Pavlos, Choueiri, Toni K, Viswanathan, Srinivas R, Sircar, Kanishka, Albiges, Laurence, Malouf, Gabriel G, Tannir, Nizar M
• Format: Article
• Language: English
• Subjects: Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - genetics; Genitourinary Cancer; Humans; In Situ Hybridization, Fluorescence; Kidney Neoplasms - drug therapy; Kidney Neoplasms - genetics; Retrospective Studies; Vascular Endothelial Growth Factor A - genetics
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1093/oncolo/oyac262

Background There remains a paucity of data regarding the efficacy of immune checkpoint therapy (ICT) combinations ± vascular endothelial growth factor (VEGF) targeted therapy (TT) in translocation renal cell carcinoma (tRCC). Methods This is a retrospective study of patients with advanced tRCC treated with ICT combinations at 11 centers in the US, France, and Belgium. Only cases with confirmed fluorescence in situ hybridization (FISH) were included. Objective response rates (ORR) and progression-free survival (PFS) were assessed by RECIST, and overall survival (OS) was estimated by Kaplan-Meier methods. Results There were 29 patients identified with median age of 38 (21-70) years, and F:M ratio 0.9:1. FISH revealed TFE3 and TFEB translocations in 22 and 7 patients, respectively. Dual ICT and ICT + VEGF TT were used in 18 and 11 patients, respectively. Seventeen (59%) patients received ICT combinations as first-line therapy. ORR was 1/18 (5.5%) for dual ICT and 4/11 (36%) for ICT + VEGF TT. At a median follow-up of 12.9 months, median PFS was 2.8 and 5.4 months in the dual ICT and ICT + VEGF TT groups, respectively. Median OS from metastatic disease was 17.8 and 30.7 months in the dual ICT and ICT + VEGF TT groups, respectively. Conclusion In this retrospective study of advanced tRCC, limited response and survival were seen after frontline dual ICT combination therapy, while ICT + VEGF TT therapy offered some efficacy. Due to the heterogeneity of tRCC, insights into the biological underpinnings are necessary to develop more effective therapies. This article evaluates the clinical activity of immune checkpoint therapy combinations with or without VEGF targeted therapy in patients with translocation renal cell carcinoma.