Evaluation of homologous recombination deficiency (HRD) status with pathological response to carboplatin +/- veliparib in BrighTNess, a randomized phase 3 study in early stage TNBC.

519Background: HRD status is significantly associated with a higher rate of response to neoadjuvant platinum-based therapy and improved PFS following adjuvant doxorubicin and cyclophosphamide (AC) in TNBC. We assessed the prognostic and predictive role of the HRD assay for platinum and PARP inhibitor response in BrighTNess. Methods: 634 stage II-III TNBC pts were randomized 2:1:1 to: Arm A: Paclitaxel (T) q wk x 12 + carboplatin (P) (AUC 6) q3 wk x 4 + veliparib (TPV) - > AC q2-3 wk x 4; Arm B: T + P + placebo (TP) - > AC; or Arm C: T + dual placebo (T) - > AC. HRD status was defined as HRD+ (HRD score ≥ 42 or a tumor BRCA1/2 mutation) or HRD- (HRD score < 42 and no tumor BRCA1/2 mutation). An exploratory HRD threshold of ≥ 33 vs < 33 was also assessed. Results: HRD status was available for 438 pts. HRD data by arm for pCR for the 42 and 33 cut-offs are shown. Within each arm using the 42 and 33 cut-offs, respectively, ORs for pCR by HRD status (HRD+/HRD-) were 2.85 (p = 0.0005) and 3.10 (p = 0.004) for A...