Phase 3 study evaluating efficacy and safety of veliparib (V) plus carboplatin (Cb) or Cb in combination with standard neoadjuvant chemotherapy (NAC) in patients (pts) with early stage triple-negative breast cancer (TNBC).

Abstract

520 Background: Clinical studies suggest that TNBC is sensitive to DNA-damaging agents, including Cb. V is a potent PARP inhibitor that may enhance the antitumor activity of such agents. We present primary response data from a phase 3 randomized, placebo-controlled study (NCT02032277) evaluating the addition of V + Cb or Cb to neoadjuvant paclitaxel (P) followed by doxorubicin + cyclophosphamide (AC). Methods: Pts with histologically confirmed, invasive TNBC (T2–T4 N0–2 or T1 N1–2) amenable to surgical resection were randomized 2:1:1 to (Arm A) P 80 mg/m2 weekly + Cb AUC 6 mg/mL/min q3 weeks + V 50 mg PO BID; (Arm B) P + Cb + PO placebo; or (Arm C) P + IV placebo + PO placebo, for 12 weeks followed by AC (60 mg/m2 or 600 mg/m2 q2 or 3 weeks) × 4. Primary endpoint was pathologic complete response (pCR) in breast and nodes with > 80% power at 2-sided α of 0.05 using pair-wise comparisons for A vs B and A vs C to detect significant treatment effects using Χ2 test; secondary endpoint was rate of conversion to eligibility for breast conservation surgery (BCS). Adverse events (AEs) were assessed with NCI CTCAE V4.0. Results: Six hundred thirty-four pts (median age 50 years; range 22–79) were randomized to Arms A (n = 316), B (n = 160), or C (n = 158). Baseline characteristics were well balanced. No pCR difference was observed between Arms A and B (53.2% vs 57.5% p = 0.36), but pCR in Arm A was higher than Arm C (53.2% vs 31.0% p < 0.001). In non-prespecified analysis, pCR in Arm B was also higher than Arm C (57.5% vs 31.0% p < 0.001). Among pts ineligible for BCS at screening (n = 141), 62% were eligible after NAC in Arm A vs 44% each in Arms B (p = 0.13) and C (p = 0.14). Grade 3–4 AEs (Arms A/B/C, 86%/85%/45%) and serious AEs (30%/27%/14%) neutropenia, thrombocytopenia, anemia, nausea, and vomiting were increased with the addition of Cb; V did not impact toxicity. Median cycles of NAC were not reduced with V + Cb + P or Cb + P vs P. Conclusions: Addition of V to neoadjuvant Cb + P followed by AC did not increase pCR rate in breast and nodes in stage II–III TNBC, while addition of V + Cb or Cb alone to P followed by AC did. Cb (+/– V) increased toxicity but did not impact delivery of NAC. Clinical trial information: NCT02032277.