Veliparib (V) monotherapy (monoTx) following combination therapy with V + carboplatin/paclitaxel (CP) in patients with gBRCA-associated advanced breast cancer: Exploratory results from BROCADE3.

Authors

null

Hyo S. Han

Moffitt Cancer Center, Tampa, FL

Hyo S. Han , Banu Arun , Bella Kaufman , Hans Wildiers , Michael Friedlander , Jean-Pierre M. Ayoub , Shannon L Puhalla , Bruce Allen Bach , Matthew Dudley , Madan Gopal Kundu , David Maag , Christine Ratajczak , Veronique Dieras

Organizations

Moffitt Cancer Center, Tampa, FL, The University of Texas MD Anderson Cancer Center, Houston, TX, Sheba Medical Center, Tel Hashomer, Israel, University Hospitals Leuven, Leuven, Belgium, Prince of Wales Clinical School University of New South Wales, and Prince of Wales Hospital, Sydney, Australia, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada, University of Pittsburgh Medical Center Cancer Centers, Pittsburgh, PA, AbbVie Inc., North Chicago, IL, Institut Curie Paris, and Centre Eugène Marquis, Rennes, France

Research Funding

Pharmaceutical/Biotech Company
AbbVie

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 gBRCA1/2 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/m2) 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.

Median PFS (investigator-assessed) in pts who received V/PL monoTx.

Cycles of C and/or P before monoTxV + CPPL + CPV + CPPL + CPHR
(95% CI)
Events, n/N at risk
(%)
Median PFS, mo
(95% CI)
≤615 / 27
(56)
12 / 13 (92)18.4
(12.5, -)
12.8
(6.2, 14.7)
0.38
(0.16, 0.88)
7–1239 / 62
(63)
21 / 27 (78)18.9
(15.1, 22.3)
13.3
(10.6, 19.7)
0.54
(0.31, 0.95)
Any70 / 136 (52)45 / 58 (78)25.7
(20.5, -)
14.6
(12.8, 19.7)
0.49
(0.34, 0.73)

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Poster Session

Session Title

Breast Cancer—Metastatic

Track

Breast Cancer

Sub Track

Other Breast Cancer Subtypes

Clinical Trial Registration Number

NCT02163694

Citation

J Clin Oncol 38: 2020 (suppl; abstr 1091)

DOI

10.1200/JCO.2020.38.15_suppl.1091

Abstract #

1091

Poster Bd #

176

Abstract Disclosures