Clinical significance of circulating tumor cells (CTCs) in hormone receptor-positive (HR+) metastatic breast cancer (MBC) patients (pts) receiving letrozole (Let) or Let plus bevacizumab (Bev): CALGB 40503 (Alliance).

person Mark Jesus Mendoza Magbanua University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA info_outline Mark Jesus Mendoza Magbanua, Oleksandr Oleksandr Savenkov, Erik Asmus, Karla V. Ballman, Janet H Scott, John Park, Maura N. Dickler, Ann H. Partridge, Lisa A. Carey, Eric P. Winer, Hope S. Rugo

Authors person Mark Jesus Mendoza Magbanua University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA info_outline Mark Jesus Mendoza Magbanua, Oleksandr Oleksandr Savenkov, Erik Asmus, Karla V. Ballman, Janet H Scott, John Park, Maura N. Dickler, Ann H. Partridge, Lisa A. Carey, Eric P. Winer, Hope S. Rugo Organizations University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, Weill Medical College of Cornell University, New York, NY, Mayo Clinic, Rochester, MN, Weill Cornell Medicine, New York, NY, University of California San Francisco, San Francisco, CA, University of California, San Francisco, San Francisco, CA, Memorial Sloan Kettering Cancer Center, New York, NY, Dana-Farber Cancer Institute, Boston, MA, University of North Carolina, Chapel Hill, NC, University of California San Francisco Comprehensive Cancer Center, San Francisco, CA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: CALGB 40503 randomized HR+ MBC postmenopausal pts to Let alone or Let+Bev as first-line therapy. Adding Bev to Let prolonged progression-free survival (PFS) but not overall survival (OS) (Dickler JCO 2016). We performed a correlative study to assess prognostic and predictive value of CTCs in this population. Methods: Blood was collected prior to initiation of treatment. CTCs were enumerated using US FDA-cleared CellSearch assay; samples with ≥5 CTCs per 7.5 mLs of blood were considered CTC-positive (CTC+). Correlation of CTCs with PFS and OS was assessed using Cox regression analysis. Median follow-up was 39 months (mo). Results: Of 343 pts treated, 294 had CTC data and were included in this analysis. Original study results that showed improved PFS (HR = 0.75; 95% CI: 0.59-0.96) but not OS (HR = 0.87; 95% CI: 0.65-1.18) in pts receiving Let+Bev compared to Let were recapitulated in this subset. In multivariable analysis, CTC+ pts (31%) had significantly reduced PFS (HR = 1.49; 95% CI: 1.12-1.97) and OS (HR = 2.08; 95% CI: 1.49-2.93) compared to CTC- pts. Moreover, CTC+ pts who did not receive Bev had worse PFS (HR = 2.31; 95% CI: 1.54-3.47) and OS (HR = 2.64; 95% CI: 1.59-4.40) (Table). CTC+ pts who received Bev had numerically longer median PFS (18.0 vs. 7.0 mo) and OS (33.6 vs. 27.1 mo) compared to CTC+ pts with no Bev; however, tests for interaction between CTC status and Bev (yes vs. no) were not statistically significant for PFS (p=0.70) or OS (p=0.84). Conclusions: CTCs were highly prognostic in this study involving addition of Bev to first-line Let in postmenopausal HR+ MBC. Further research to determine the potential predictive value of CTCs in the setting of both metastatic disease and early breast cancer is warranted. Support: U10CA180821, U10CA180882; Genentech; https://acknowledgments.alliancefound.org; NCT00601900. Survival in HR+ MBC pts receiving Let or Let+Bev stratified by CTC status. Clinical trial information: NCT00601900 Total Events Median survival in mo (95% CI) Adjusted Hazard Ratio (95% CI) Adjusted Likelihood-Ratio p-value PFS 0.0012 CTC-: Let+Bev 108 70 18.4 (15.0-23.5) 1.0 CTC-: Let 94 74 14.7 (11.4-18.9) 1.44 (1.02-2.02) CTC+: Let+Bev 46 42 18.0 (13.6-23.7) 1.44 (0.98-2.13) CTC+: Let 46 38 7.0 (2.8-10.9) 2.31(1.54-3.47) OS 0.0003 CTC-: Let+Bev 108 35 49.1 (42.4-NE) 1.0 CTC-: Let 94 44 45.0 (40.1-50.1) 1.29 (0.82-2.03) CTC+: Let+Bev 46 34 33.6 (26.6-40.0) 2.20 (1.37-3.55) CTC+: Let 46 28 27.1 (20.6-36.1) 2.64 (1.59-4.40)