Pharma Update
Giredestrant data support potential in 1L and adj HR+ BC
Tumor response is correlated with higher tumor ER activity
sample collection
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In eBC, 1L, and ESR1m patients, the tumor is ER pathway dependent
2023 ASCO
ANNUAL MEETING
2022 ASCO
ANNUAL MEETING
Tumor ER pathway activity by time of
Ph II (coopERA) results in neoadj setting
ო
Ki67 response at wk 2 and at surgery
Relative reduction in Ki67% from baseline
Baseline to week 2
Giredestrant
(n = 107).
-75%
Anastrazole
(n=94)
-67%
Baseline to surgery
G+P
(n = 93)
-81%
A+ P
(n=91)
-74%
ER activity Z-score
Т
C
N
୯
eBC
pre-1L
post-1L post-1L
ESR1wt ESR1m
0.00
-0.25-
-0.50-
-0.75-
-1.00-
o
G+P, Giredestrant + Palbociclib; A+P, Anastrozole + Palbociclib
PFS-INV, %
Ph II acelERA results in 2/3L setting
PFS-INV: ESR1m subgroup
giredestrant
(n=51)
Roche
PARIS
ESMO
Congress
2022
100
PCET
(n = 39)
90-
HR (95% CI)
80-
p-value (log-rank)
mPFS, months
0.60 (0.35, 1.03)
0.0610
5.3
3.5
70-
60-
50-
40-
30-
20-
10-
0
0
6
8
10
12
14
Months
Exploratory biomarker analysis of acelERA: Post 1L treatment, ER activity was maintained in patients with ESR1m tumors at levels similar to early BC and pre-
1L, while activity was significantly lower in late-line patients with no ESR1 mutation
•
•
Ph II (coopERA) in neoadjuvant setting: Final analysis confirmed greater suppression of Ki67 and rates of complete cycle arrest with giredestrant vs.
anastrazole at time of surgery; Ki67 is a biomarker of proliferation associated with improved long-term efficacy outcomes in early stage disease
⚫ Ph II (acelERA) in 2/3L setting: PFS benefit more pronounced in patients with baseline ESR1 mutations (HR 0.61 in ESR1m patients vs. HR 0.81 in all-comers)
•
Majority of 2L/3L patients appear to be no longer sensitive to endocrine inhibition but ESR1m patients' tumors are still dependent on ER signaling
Collier A. et al., ASCO 2023; Fasching P. et al., ASCO 2022; Martin M. et al., ESMO 2022; adj-adjuvant; ORR=objective response rate; PFS=progression-free survival; HR-hazard ratio; HR+=Hprmone receptor positive;
ER=estrogen receptor; eBC-early breast cancer; m=months; Cl=confidence interval; ESR1-estrogen receptor 1
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