2024-SABCS-Takeaways - 5

 OlympiA
The EMBER-3 trial (GS1-01)
found that the oral selective
estrogen receptor degrader (SERD)
imlunestrant can provide an all-oral
targeted therapy option for adults
with estrogen receptor (ER)-positive,
HER2-negative advanced breast
cancer who had received prior
therapy with an aromatase inhibitor
(with or without a CDK4/6 inhibitor).
Imlunestrant significantly improved
progression-free survival compared
to standard-of-care fulvestrant or
exemestane for patients with ESR1
mutations and for all patients when
combined with abemaciclib.
See EMBER-3 at right 
The PATINA trial (GS2-12)
produced practice-changing data
for patients with HR-positive,
HER2-positive metastatic
breast cancer without disease
progression after completing
induction chemotherapy. The
study showed clinically meaningful
improvement in progression-free
survival (PFS) of 44.3 months for
combination therapy of palbociclib
with anti-HER2 therapy and ET
compared to 29.1 months for antiHER2
therapy and ET alone. OS
data remains immature.
The effects of obesity on breast
cancer recurrence were examined
in a meta-analysis of
more than 200,000
women in 147 trials by
the Early Breast Cancer
Trialists' Collaborative
Group (GS2-09) The
study found patients
with a BMI ≥30 had a
recurrence rate ratio
of 1.17 compared to
patients with a BMI <25.
The association of BMI
with distant recurrence
was independent of
systemic therapy and
ER status. The authors
concluded that a
randomized assessment
of weight-loss interventions,
potentially including GLP-1 receptor
agonists, would be useful in a future
clinical trial.
Lifestyle intervention is difficult
for patients and weight loss is
seldom durable. The BWEL trial
(RF1-01) found positive changes
in insulin, leptin, and C-reactive
protein associated with weight loss
and smaller waist circumference,
but potential correlations with
cancer outcomes have not yet
been analyzed.
Molecular residual disease (MRD),
formerly referred to as minimal
residual disease, may be a useful
CLICK TO EXPAND
 EMBER-3
CLICK TO EXPAND
tool, but the ZEST circulating
tumor DNA (ctDNA) trial (GS3-01)
in TNBC with MRD was terminated
early due to infeasibility of
completing enrollment. This phase
III randomized trial of MRD-directed
therapy compared niraparib to
placebo for TNBC or HER2-negative
BRCA-mutated breast cancer
with no evidence of radiographic
occurrence after treatment. A high
rate of radiographic recurrence
at ctDNA detection supported
the concept of MRD as well as
strategies calling for ctDNA
testing to begin earlier in the
disease trajectory. 
ON BUILDING NOVEL EFFECTIVE COMBINATIONS
" Potency and specificity matter. The best drug for the eventual
combination might not be the best drug as monotherapy. "
WILLIAM G. KAELIN, JR, MD, Nobel Laureate and Sidney Farber Professor of Medicine,
Dana-Farber Cancer Institute
December 10-13, 2024 | San Antonio, Texas
5
2024-SABCS-Takeaways

Table of Contents for the Digital Edition of 2024-SABCS-Takeaways
