In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 1091-1091
Abstract:
1091 Background: In BROCADE3 (NCT02163694), addition of PARP inhibitor V to CP resulted in improved progression-free survival (PFS) (HR 0.71 [95% CI 0.57−0.88], p=0.002) in patients (pts) with advanced HER2-negative breast cancer and g BRCA1/2 mutation. A subset of pts transitioned to V/placebo (PL) monoTx at an intensified dose/schedule after CP discontinuation prior to progression (investigator discretion). Here, we evaluate the impact of this transition on efficacy and safety. Methods: Pts were randomized 2:1 to CP with V (n=337) or PL (n=172). V (120 mg po BID) or PL was given on Days (D) −2 to 5, C (AUC 6) on D1, and P (80 mg/m 2 ) on D1, 8, and 15 (21-day cycles). Pts who transitioned to monoTx received V/PL 300-400mg BID daily until progression. A Cox model with a time varying covariate indicating transition from V/PL with CP to V/PL monoTx was fit to estimate treatment effect during combination and monoTx phases. PFS by cycles of CP prior to monoTx and AEs during monoTx are summarized. Results: A subgroup of 136 (40%) and 58 (34%) pts on the V and PL arms, respectively, received monoTx. When a Cox model with a time-varying covariate was fit for PFS (per investigator), the nominal P-value for treatment by covariate interaction was 0.038. The HRs (95% CI) for V vs PL during combination therapy and monoTx were 0.81 (0.62–1.06) and 0.49 (0.33–0.73). The Table summarizes PFS by cycles of C and/or P prior to monoTx. Common AEs ( 〉 20% of pts) during V or PL monoTx were nausea (52%/10%), fatigue (23%/12%), headache (21%/17%), and diarrhea (21%/9%). Seizures (2.2%/0%) were reported during monoTx. Rates of cytopenias for V or PL monoTx were: anemia 12%/14%; neutropenia 13%/12%; and thrombocytopenia 10%/5%. Conclusions: These analyses suggest that pts treated with V + CP derive benefit from both combination therapy as well as V monoTx after CP discontinuation. Pts receiving V monoTx after ≤ 6 cycles of VCP experienced a similar benefit to those who transitioned to monoTx after 7–12 cycles of VCP, suggesting that V maintenance therapy may be suitable following a limited duration of combination therapy. Clinical trial information: NCT02163694 . [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.1091
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
