Details

Autor(en) / Beteiligte

• Borkowetz, Angelika
• Sommer, Ulrich
• Baretton, Gustavo
• Gruellich, Carsten
• Bürk, Björn Thorben
• Erb, Holger H. H.
• Thomas, Christian

Titel

Identification of genomic drivers for the therapeutic response of Cabozantinib in patients with metastatic renal cell carcinoma

Ist Teil von

• World journal of urology, 2024-02, Vol.42 (1), p.94-94, Article 94

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2024

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Purpose Cabozantinib (CAB) as monotherapy or in combination with immune checkpoint inhibitors is used for systemic treatment of metastatic renal cell carcinoma (mRCC). However, little is known about predictors of treatment response to CAB. For this reason, known genomic drivers were examined to identify potential predictors of treatment response with CAB. Methods Twenty mRCC patients receiving monotherapy (≥ first-line) with CAB were prospectively included. DNA was extracted from archived primary tumors or metastatic tissue. Targeted DNA sequencing was performed using a gene panel including 328 genes (QIAseq Targeted DNA V3 Panel, Qiagen). The variant evaluation was performed using Varsome. The endpoints were treatment-failure-free-survival (TFFS) to CAB. Results 26% of patients received systemic RCC treatment as the primary option. Six patients were treated with CAB in first-line (1L) and 12 patients in ≥ 2L. The median follow-up after initiation of systemic treatment was 26.7 months (mo). The PBRM1 (7 alleles), SETD2 (7 alleles), VHL (11 alleles), and CHEK2 (14 alleles) genes were most frequently altered. The median time to TFFS was 10.5 mo (95% confidence interval (CI) 6.2–14.7 mo). There was a longer treatment response to CAB in patients with alterations of the SETD2 gene ( SETD2 alteration median TFFS not reached vs. no SETD2 alterations 8.4 mo (95% CI 5.2–11.6 mo); p  = 0.024). Conclusion Pathogenic variant genes may indicate treatment response to systemic therapy in mRCC. Patients with alterations of the SETD2 gene show longer responses to CAB treatment.