SABCS 2013 S5-02: Veliparib/Carboplatin Plus Standard Neoadjuvant Therapy for High-Risk Breast Cancer: First Efficacy Results From the I-SPY 2 Trial. HS. Rugo et al.
Background: I-SPY 2 is a multicenter, phase 2 screening trial using adaptive randomization within biomarker subtypes to evaluate a series of novel agents/combinations when added to standard neoadjuvant therapy (paclitaxel q wk x 12, doxorubicin & cyclophosphamide q 2-3 wk x 4, T/AC) vs. T/AC (control arm) for women with high-risk stage II/III breast cancer. The primary endpoint is pathologic complete response (pCR in breast and axilla) at surgery. The goal is to identify/graduate regimens that have ≥ 85% Bayesian predictive probability of success (statistical significance) in a 300-patient biomarker-linked phase 3 neoadjuvant trial. Experimental regimens can "graduate" in at least 1 of 10 possible signatures defined by hormone-receptor (HR) & HER2 status and MammaPrint (MP) classification, with a maximum number of 120 total patients enrolled per arm. This is the first report from 1-SPY 2, which is the efficacy results of the oral PARP inhibitor veliparib (V, ABT-888) at 50 mg PO BID in combination with carboplatin (Cb) AUC 6 q 3 weekly x 4 with weekly paclitaxel.
Conclusions: 72 patients were randomized to receive veliparib/Cb and standard chemotherapy while 62 patients were randomized to the standard chemotherapy (control) arm. In the HER2-negative population, the estimated pCR rate was 33% (V + Cb) vs. 22% (control). Adaptive randomization successfully identified a biomarker signature for V + Cb. The estimated pCR rate for V + Cb was 52% (95% CI: 35%–69%) versus 26% (95% vCI: 11%–40%) for the control arm in the triple-negative breast cancer signature. and is the subset recommended for this regimen's subsequent development. The estimated probability of success for this combination in a phase 3 trial is 90%.Greater hematological toxicity was seen in the V + Cb arm, with subsequent dose reductions required in the 49% of cases with carboplatin and in 27% with the paclitaxel dose. A slight delay (17 days median) from treatment to surgery was also seen in the combination arm.