Circulating tumor cell (CTC) enumeration in patients (pts) with metastatic genitourinary (mGU) tumors treated in a phase I study of cabozantinib and nivolumab (CaboNivo) +/- ipilimumab (CaboNivoIpi).

Andrea B. Apolo Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD info_outline Andrea B. Apolo, Amir Mortazavi, Zishuo Ian Hu, Joseph Schonhoft, Lincy Chu, Amanda K. L. Anderson, Yipeng Wang, Ryan Dittamore, Sumanta K. Pal, Primo Lara, Mark N. Stein, Seth M. Steinberg, Christian Mayfield, Lisa M. Cordes, Marissa Mallek, Rene Costello, Carlos Diaz, Jane B Trepel, Donald P. Bottaro

Authors Andrea B. Apolo Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD info_outline Andrea B. Apolo, Amir Mortazavi, Zishuo Ian Hu, Joseph Schonhoft, Lincy Chu, Amanda K. L. Anderson, Yipeng Wang, Ryan Dittamore, Sumanta K. Pal, Primo Lara, Mark N. Stein, Seth M. Steinberg, Christian Mayfield, Lisa M. Cordes, Marissa Mallek, Rene Costello, Carlos Diaz, Jane B Trepel, Donald P. Bottaro Organizations Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, Arthur G. James Cancer Hospital, Ohio State University Wexner Medical Center, Columbus, OH, Stony Brook Hospital, Stony Brook, NY, Epic Sciences, Inc., San Diego, CA, Epic Sciences, San Diego, CA, City of Hope National Medical Center, Duarte, CA, University of California, Davis, Sacramento, CA, Columbia University Medical Center, New York, NY, Biostatistics and Data Management Section, NCI, NIH, Bethesda, MD, National Cancer Institute, National Institutes of Health, Bethesda, MD, National Institutes of Health, Bethesda, MD, National Cancer Institute, Bethesda, MD, Center for Cancer Research, NCI, NIH, Bethesda, MD, Center for Cancer Research, Division of Cancer Treatment and Diagnosis, Bethesda, MD Abstract Disclosures Research Funding U.S. National Institutes of Health Background: CTCs may serve as biomarkers for clinical outcomes in GU tumor pts. We examined the association between baseline CTC enumeration, CTC heterogeneity, CTC morphologic subtypes, and progression-free-survival, overall survival and response to therapy with combination CaboNivo or CaboNivoIpi. Methods: 123 samples from 52 pts with mGU tumors treated with CaboNivo (38 pts) or CaboNivoIpi (14 pts) drawn at Baseline, Cycle (C) 2 Day (D) 1, and C3D1 were processed using the Epic Sciences platform. CTCs were defined as cytokeratin (CK)+, CD45-, distinct morphology, intact nucleus. PD-L1 expression was also assessed. Results: From 07/20/2016-09/01/2018, 52 pts [urothelial carcinoma (UC) N = 33; plasmacytoid N = 1; Clear cell renal cell carcinoma N = 4; bladder adenocarcinoma N = 8; bladder squamous cell carcinoma N = 2; bladder small cell N = 2; renal medullary N = 2] were treated. Median age was 61.5 years (range 20-82); 35 (67%) were male. N = 37 (71%) had visceral involvement, N = 15 (29%) with liver involvement, N = 11 (21%) with bone involvement. CTCs were found in the peripheral blood of 26/40 (65%) pts at baseline. 1/40 pts (bladder adenocarcinoma) had PDL1+ CTCs at Baseline. Median CTC/mL at Baseline, C2D1, C3D1, were not significantly different. CTC counts of > 2 and > 4 at C2D1 were potentially associated with shorter OS (p = 0.071 and p = 0.045 without adjustment for multiple cutoffs for evaluation). PFS results exhibited similar trends. Unsupervised clustering of CTC images identified 5 main CTC subtypes, of which the presence of one was significantly associated with shorter OS (p = 0.0014, not adjusted for multiple testing). Additionally, we observed a trend towards patients with higher CTC heterogeneity at C2D1 having longer OS, when adjusting for the risk associated with CTC enumeration (p = 0.084). Conclusions: CTC were detected in pts with mGU tumors treated with CaboNivo and CaboNivoIpi. CTC values were somewhat but not statistically lower in responders vs. non-responders. On treatment lower CTCs and the absence of aggressive CTC subtypes were associated with better clinical outcomes. Ongoing analyses include single cell genomics, and analysis of T-cell populations. Clinical trial information: NCT02496208