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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F18%3A00078081" target="_blank" >RIV/00209805:_____/18:00078081 - isvavai.cz</a>

Výsledek na webu

<a href="https://academic.oup.com/annonc/article/29/1/154/4282670" target="_blank" >https://academic.oup.com/annonc/article/29/1/154/4282670</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/annonc/mdx505" target="_blank" >10.1093/annonc/mdx505</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 patientsGREATER-THAN OR EQUAL TO18 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&lt;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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 patientsGREATER-THAN OR EQUAL TO18 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&lt;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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Annals of oncology

ISSN

0923-7534

e-ISSN

—

Svazek periodika

29

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

8

Strana od-do

154-161

Kód UT WoS článku

000423741500024

EID výsledku v databázi Scopus

2-s2.0-85041174932