The genomic landscape of metastatic clear cell renal cell carcinoma (ccRCC) after treatment with systemic therapy.

• DOI: 10.1200/jco.2019.37.7_suppl.675
• Publication Date: 2019-03-07T21:30:11Z
• Authors: Johannes Van Der ...; Kenneth Eng; Evan Fernandez; Clara Oromendia; Tuo Zhang; Rohan Bareja; Sinan Ramazanoglu; Aram Vosoughi; Lorraine J. Gudas.; Olivier Elemento; Scott T. Tagawa; Bishoy Morris Faltas; David M. Nanus; Himisha Beltran; Juan Miguel Mosquera; Andrea Sboner; Ana M. Molina
• Keywords: Targeted Therapy; Systemic therapy; Immune checkpoint

675 Background: The most frequent genomic alterations in patients (pts) with ccRCC have been identified primary tumors. Here we investigated the landscape of a cohort enriched for metastatic tumors after treatment systemic therapy. Methods: We prospectively enrolled pts clinical study which Whole-Exome Sequencing (WES) normal and tumor tissue was performed. Clinical features, outcome survival were evaluated. Results: Forty-five median age 65 years (range 38–86) enrolled. According to Heng risk criteria, 15 (33.3%) classified as favorable-risk 23 (51.1%) intermediate-risk 7 (15.6%) poor-risk. Pts received number 3 lines 0–9) therapy including cytokines (n=7), anti-VEGF (n=36), mTOR inhibitors (n=10) and/or immune checkpoint (n=23). progression free (PFS) 3.5 months (0.7-13.1), 11.1 (1.1–54.2), 2.7 (0.7-36.2) 4.9 (1.4–29.2) cytokines, VEGF-, mTOR- inhibitors, respectively. overall (OS) from start last follow up 2.2 0.2–14.9 years). A total 68 samples sequenced. These included 9 (12.5%) tumors, 38 (55.9%) collected anti-VEGF, 16 (23.5%) 8 (11.8%) inhibitor. VHL, KDM5C, SETD2 PBRM1 somatic mutations detected this cohort. In two cases short long response VEGF targeted (PFS 2.8 versus 50.3 months) rapid autopsies performed allowed multiregional (n=7, n=4) sampling. sequencing autopsy case prolonged revealed recurrent KDM5C mutations. Conclusions: present report an increased frequency mutations, previously described be associated favorable VEGF-inhibitors.