Practice Update: Oncology

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MONARCH 3: Abemaciclib Improves Progression-Free Survival
in Endocrine-Sensitive Advanced Breast Cancer
Although most women benefited substantially from the addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor
abemaciclib as initial treatment for endocrine-sensitive advanced breast cancer, with extended progression-free
survival, approximately one-third of women may not need a CDK 4/6 inhibitor as initial treatment. The findings from the
18-month interim analysis of the phase III, randomized, double-blind MONARCH 3 trial of abemaciclib vs placebo were
reported at the European Society for Medical Oncology (ESMO) 2017 Congress, from September 8–12.
In MONARCH 3, led by Angelo Di Leo,
MD, PhD, of the Hospital of Prato, Isti-
tuto Toscano Tumori, Italy, abemaciclib
or placebo was added to endocrine ther-
apy with a nonsteroidal aromatase inhibitor
(anastrozole or letrozole) as initial therapy
in postmenopausal women with hormone
receptor-positive, human epidermal
growth factor receptor 2 (HER2)-negative
advanced breast cancer.
A total of 493 patients from 22 countries
who had never been treated for metastatic
disease were included in the analysis.
Compared with single-agent endocrine
therapy alone, the addition of abemaciclib
significantly increased the primary end-
point of progression-free survival (hazard
ratio 0.543 [P = .000021]).
In patients with measurable disease, the
objective response rate was 59% with
abemaciclib vs. 44% in with placebo (P =
.004).
The most common adverse events
were diarrhea and neutropenia, which
occurred in 81.3% and 41.3%, respectively
with abemaciclib vs. 29.8% and 1.9% with
placebo.
In a written release from ESMO, Dr. Di Leo
noted that MONARCH 3 is the third study
to demonstrate that the combination of
endocrine therapy with a CDK4/6 inhibi-
tor is better than endocrine therapy alone,
with abemaciclib reducing the risk of dis-
ease progression by 46%.
He added that the data also showed that it
may be possible to better distinguish ben-
efits among groups of patients. In patients
with more challenging disease character-
istics, such as liver metastases, patients
benefited substantially from the addition
of abemaciclib. By contrast, in subgroups
with bone metastases only or with indolent
disease that relapsed years after stopping
adjuvant endocrine therapy, endocrine
therapy alone conferred an excellent
prognosis.
According to Dr. Di Leo, for the first time,
data suggest that patients with certain clin-
ical characteristics may benefit differently
from treatment with a CDK 4/6 inhibitor.
Some patients with a good prognosis
may be able to receive endocrine ther-
apy alone, and CDK 4/6 inhibitors could
be reserved as a next line of treatment for
metastatic disease, an idea that warrants
further investigation.
Nearly one-third of patients had bone
metastases only or a tumor that relapsed
several years after stopping adjuvant endo-
crine therapy. Dr. Di Leo pointed out that
this is a clinically relevant proportion of
patients, and in these patients, the use
of a CDK 4/6 inhibitor could be delayed,
which would minimize costs and decrease
toxicity.
Giuseppe Curigliano, MD, of the Euro-
pean Institute of Oncology, University of
Milan, Italy, stated in the written release that
abemaciclib is the third CDK 4/6 inhibitor to
be evaluated in advanced breast cancer.
MONARCH 3 confirms the role of this new
class of agents in combination with endo-
crine therapy for metastatic breast cancer.
He added that many patients with meta-
static disease still receive chemotherapy,
despite guidelines and data from clinical
trials. The interim results from this study
suggest that chemotherapy should be
avoided in hormone receptor-positive,
HER2-negative metastatic breast cancer
in the absence of visceral crisis.
Dr. Curigliano suggested that an academ-
ic-driven trial should address questions
about the optimal sequencing of endocrine
therapy and CDK 4/6 inhibitors.
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