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Veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in patients with BRCA1/2 locally recurrent/metastatic breast cancer: randomized phase II study.

Publication ,  Journal Article
Han, HS; Diéras, V; Robson, M; Palácová, M; Marcom, PK; Jager, A; Bondarenko, I; Citrin, D; Campone, M; Telli, ML; Domchek, SM; Friedlander, M ...
Published in: Ann Oncol
January 1, 2018

BACKGROUND: Homologous recombination defects in BRCA1/2-mutated tumors result in sensitivity to poly(ADP-ribose) polymerase inhibitors, which interfere with DNA damage repair. Veliparib, a potent poly(ADP-ribose) polymerase inhibitor, enhanced the antitumor activity of platinum agents and temozolomide in early phase clinical trials. This phase II study examined the safety and efficacy of intermittent veliparib with carboplatin/paclitaxel (VCP) or temozolomide (VT) in patients with BRCA1/2-mutated breast cancer. PATIENTS AND METHODS: Eligible patients ≥18 years with locally recurrent or metastatic breast cancer and a deleterious BRCA1/2 germline mutation were randomized 1 : 1 : 1 to VCP, VT, or placebo plus carboplatin/paclitaxel (PCP). Primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and overall response rate (ORR). RESULTS: Of 290 randomized patients, 284 were BRCA+, confirmed by central laboratory. For VCP versus PCP, median PFS was 14.1 and 12.3 months, respectively [hazard ratio (HR) 0.789; 95% CI 0.536-1.162; P = 0.227], interim median OS 28.3 and 25.9 months (HR 0.750; 95% CI 0.503-1.117; P = 0.156), and ORR 77.8% and 61.3% (P = 0.027). For VT (versus PCP), median PFS was 7.4 months (HR 1.858; 95% CI 1.278-2.702; P = 0.001), interim median OS 19.1 months (HR 1.483; 95% CI 1.032-2.131; P = 0.032), and ORR 28.6% (P < 0.001). Safety profile was comparable between carboplatin/paclitaxel arms. Adverse events (all grades) of neutropenia, anemia, alopecia, and neuropathy were less frequent with VT versus PCP. CONCLUSION: Numerical but not statistically significant increases in both PFS and OS were observed in patients with BRCA1/2-mutated recurrent/metastatic breast cancer receiving VCP compared with PCP. The addition of veliparib to carboplatin/paclitaxel significantly improved ORR. There was no clinically meaningful increase in toxicity with VCP versus PCP. VT was inferior to PCP. An ongoing phase III trial is evaluating VCP versus PCP, with optional continuation single-agent therapy with veliparib/placebo if chemotherapy is discontinued without progression, in this patient population. CLINICAL TRIAL INFORMATION: NCT01506609.

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Published In

Ann Oncol

DOI

EISSN

1569-8041

Publication Date

January 1, 2018

Volume

29

Issue

1

Start / End Page

154 / 161

Location

England

Related Subject Headings

  • Young Adult
  • Temozolomide
  • Single-Blind Method
  • Placebos
  • Paclitaxel
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Neoplasm Metastasis
  • Middle Aged
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
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Han, H. S., Diéras, V., Robson, M., Palácová, M., Marcom, P. K., Jager, A., … Puhalla, S. (2018). Veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in patients with BRCA1/2 locally recurrent/metastatic breast cancer: randomized phase II study. Ann Oncol, 29(1), 154–161. https://doi.org/10.1093/annonc/mdx505
Han, H. S., V. Diéras, M. Robson, M. Palácová, P. K. Marcom, A. Jager, I. Bondarenko, et al. “Veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in patients with BRCA1/2 locally recurrent/metastatic breast cancer: randomized phase II study.Ann Oncol 29, no. 1 (January 1, 2018): 154–61. https://doi.org/10.1093/annonc/mdx505.
Han HS, Diéras V, Robson M, Palácová M, Marcom PK, Jager A, Bondarenko I, Citrin D, Campone M, Telli ML, Domchek SM, Friedlander M, Kaufman B, Garber JE, Shparyk Y, Chmielowska E, Jakobsen EH, Kaklamani V, Gradishar W, Ratajczak CK, Nickner C, Qin Q, Qian J, Shepherd SP, Isakoff SJ, Puhalla S. Veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in patients with BRCA1/2 locally recurrent/metastatic breast cancer: randomized phase II study. Ann Oncol. 2018 Jan 1;29(1):154–161.
Journal cover image

Published In

Ann Oncol

DOI

EISSN

1569-8041

Publication Date

January 1, 2018

Volume

29

Issue

1

Start / End Page

154 / 161

Location

England

Related Subject Headings

  • Young Adult
  • Temozolomide
  • Single-Blind Method
  • Placebos
  • Paclitaxel
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Neoplasm Metastasis
  • Middle Aged
  • Male