Predictive Value of Topoisomerase 1 by Immunohistochemistry (top1 Ihc) in Patients with Metastatic Breast Cancer Receiving Irinotecan-Based Therapy.

1037 Background: There is an unmet need for rapid assays predictive of efficacy for specific chemotherapy agents. In particular, for those patients with metastatic disease that have progressed on prior therapies. Newer multi-omic analysis can be performed on a single biopsy specimen and with rapid turn-around-time allowing greater clinical utility. Methods: 49 patients with measurable metastatic breast cancer (MBC) and with a history of prior treatments were enrolled in a prospective phase II study. Real-time biopsies were evaluated with a multi-omic platform which included TOP1 (1D6 antibody, positive if intensity > = 2+ in at least 30% tumor) measured by IHC. 23 of 49 tumors were TOP1 positive. Each of the 23 patients received an irinotecan based regimen as follows: 11 irinotecan alone, 9 (irinotecan+capecitabine) or (irinotecan+fluorouracil/leucovorin), 2 (irinotecan+trastuzumab) and 1 (irinotecan+exemestane). To determine therapeutics benefit, a predetermined endpoint (developed by Von Hoff, et al. JCO 2010 was used: The ratio of the progression free survival (PFS) of the new regimen divided by the PFS of the prior therapy (GMI) with a ratio of 1.3 or greater indicating improved therapeutic benefit from the new regimen. Results: Among the 23 TOP1 positive patients,13/18 evaluable patients were GMI positive (72%), 5 GMI negative, while 4 were not evaluable and 1 was too early for evaluation. In the subset of patients receiving irinotecan alone, 6/11 patients had a positive GMI (55%). Conclusions: In this prospective phase II study in patients with advanced MBC, measurement of TOP1 predicted clinical benefit as measured by GMI, in 72% of all patients receiving irinotecan based therapy and in 6/11 (55%) patients receiving irinotecan alone. These findings warrant further evaluation of TOP1 IHC in predicting the utility of irinotecan in the treatment of breast cancer. Clinical trial information: NCT01919749.