Abstract No. 
AACR 107th Annual Meeting 2016
April 16-20

Combining sensitivity markers to identify triple-negative breast cancer patients most responsive to veliparib/carboplatin: results from the I-SPY 2 TRIAL

Wolf DM, Yau C, Sanil A, Brown-Swigart L, Hirst G, Buxton M, Paoloni M, I-SPY2 TRIAL Investigators, Olopade O, Rugo H, DeMichele A, Symmans F, Berry D, Esserman, L, van t Veer, L

BACKGROUND: In the I-SPY 2 TRIAL, HER2-negative patients received standard chemotherapy alone or with the PARP inhibitor veliparib and carboplatin (VC). VC graduated in the triple-negative (TN) subtype, and we’ve previously shown that MammaPrint High1/High2 (MP1/2) risk class and the PARPi-7 signature may predict VC response. Here we evaluate whether combining these signatures identifies a subset of TN patients especially likely to respond to VC.

METHODS: This analysis includes 60 TN patients (VC: 39 and controls: 21). PARPi-7 and MP1/2 signature scores are computed from Agilent 44K arrays. We further stratify TN patients by VC-sensitivity biomarkers (MP2, PARPi7-high). We use Bayesian modeling to estimate pCR rates in each arm and the predictive probability of VC demonstrating superiority to control in a 1:1 randomized phase 3 trial of 300 ‘biomarker-positive’ patients. Our study is exploratory and does not adjust for multiplicities of biomarkers outside this study.

RESULTS: Though 90% of TNs are PARPi7-high or MP2, concordance between these biomarkers is 50%. The estimated pCR rates to VC are 69% in PARPi7-high and 64% in MP2 TN patients, compared to 53% in the entire TN subgroup. TN patients positive for both sensitivity markers (assessed as PARPi7-high and MP2) achieved an estimated pCR rate of 79% in the VC arm vs. 23% in the control arm, with a predictive probability of success in phase 3 of 99.6%. In contrast, TN patients negative for at least one VC sensitivity marker (PARPi7-low and/or MP1) only had an estimated response rate to VC of 35%.

CONCLUSION: Our analysis suggests TN patients who are also MP2 and PARPi7-high may be more sensitive to V/C than patients with fewer markers in the ‘sensitive’ state.

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