Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F18%3A00078003" target="_blank" >RIV/00209805:_____/18:00078003 - isvavai.cz</a>

Result on the web

<a href="https://academic.oup.com/annonc/article/29/7/1541/4989216" target="_blank" >https://academic.oup.com/annonc/article/29/7/1541/4989216</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/annonc/mdy155" target="_blank" >10.1093/annonc/mdy155</a>

Result language

angličtina

Original language name

Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer

Original language description

BACKGROUND: The phase III MONALEESA-2 study demonstrated significantly prolonged progression-free survival (PFS) and a manageable toxicity profile for first-line ribociclib plus letrozole versus placebo plus letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Here we report updated efficacy and safety data, together with exploratory biomarker analyses, from the MONALEESA-2 study. PATIENTS AND METHODS: A total of 668 postmenopausal women with HR+, HER2- recurrent/metastatic breast cancer were randomized (1:1; stratified by presence/absence of liver and/or lung metastases) to ribociclib (600 mg/day; 3-weeks-on/1-week-off; 28-day treatment cycles) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole. The primary endpoint was locally assessed PFS. The key secondary endpoint was overall survival (OS). Other secondary endpoints included overall response rate (ORR) and safety. Biomarker analysis was an exploratory endpoint. RESULTS:At the time of the second interim analysis, the median duration of follow-up was 26.4 months. Median PFS was 25.3 months (95% confidence interval [CI], 23.0-30.3) for ribociclib plus letrozole and 16.0 months (95% CI, 13.4-18.2) for placebo plus letrozole (hazard ratio 0.568; 95% CI, 0.457-0.704; log-rank P=9.63 x 10-8). Ribociclib treatment benefit was maintained irrespective of PIK3CA or TP53 mutation status, total Rb, Ki67, or p16 protein expression, and CDKN2A, CCND1, or ESR1 mRNA levels. Ribociclib benefit was more pronounced in patients with wild-type versus altered receptor tyrosine kinase genes. OS data remain immature, with 116 deaths observed; 50 in the ribociclib arm and 66 in the placebo arm (hazard ratio: 0.746; 95% CI, 0.517-1.078). The ORR was 42.5% versus 28.7% for all patients treated with ribociclib plus letrozole versus placebo plus letrozole, respectively, and 54.5% versus 38.8%, respectively, for patients with measurable disease. Safety results, after a further 11.1 months of follow-up, were comparable with those reported at the first analysis, with no new or unexpected toxicities observed, and no evidence of cumulative toxicity. CONCLUSIONS:The improved efficacy outcomes and manageable tolerability observed with first-line ribociclib plus letrozole are maintained with longer follow-up, relative to letrozole monotherapy. CLINICAL TRIALS NUMBER: NCT01958021.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

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

Name of the periodical

Annals of oncology

ISSN

0923-7534

e-ISSN

—

Volume of the periodical

29

Issue of the periodical within the volume

7

Country of publishing house

GB - UNITED KINGDOM

Number of pages

7

Pages from-to

1541-1547

UT code for WoS article

000438521900008

EID of the result in the Scopus database

2-s2.0-85050821270