"Personalized Treatment with Novel Medicines"

HR+/HER2- ABC

Aumkhae Sookprasert,MD
Medicine department,KKU
TH-7693 Expiration Date 31/07/2023
 1

ER, PR +
HER2+
TN
 Mechanism of
endocrine resistant
& overcoming
resistance strategy
 Mechanism of
endocrine resistant
& overcoming
resistance strategy
 Low vs High Sensitive vs Resistance
tumor burden (Clinical)

1 2 3 4

Sensitive vs Resistance
(Molecular)

When ?
Where ?
 After nearly runout of
treatment option
After first line
3
1 2
Before initiate Px
 1

3 3 (2)

4
5
 Early molecular test(s) ?
1.Predict which patient will or will not benefit from treatment
2.Early intervention to overcome resistance
 First line CDK4/6 plus hormonal therapy

Ribociclib
Palbociclib Abemaciclib

MONALEESA-3
Trial PALOMA -2 MONALEESA - 2 MONALEESA -7 MONARCH - 3
(subgroup 1st line)

With Letrozole Letrozole AI or TAM Fulvestrant Letrozole

27.6 vs 14.5 25.3 vs 16 23.8 vs 13 NR vs 18.3 28.1 vs 14.7

PFS
HR = 0.56 HR = 0.56 HR = 0.55 HR = 0.577 HR = 0.54
12
NR vs 29.7 NR vs 45.1
OS Not yet report NR vs 33 HR = 0.712 HR = 0.7 Not yet report
P=0.00973 (0.479-1.021)

ORR (%) 55.3 vs 44.4 52.7 vs 37.1 40.9 vs 29.7 NR 59 vs 44

 After nearly runout of
treatment option
After first line
3
1 2
Before initiate Px
Who might not
benefit from
adding CDK4/6
 JCO 2020

Pool analysis of phase III Ribociclib vs Placebo

Use PAM-50 to identify intrinsic subtype
PFS in Luminal A

PFS in Basal subtype

Prat A, et al. JCO 2020

Prat A, et al. JCO 2020
 Trial Population E vs C PFS OS

Mouridsen T, et al Post adjuvant TAM > 12 9.4* vs 6.0 34 vs 30

Let vs TAM
(2007) months HR = 0.72 (NS)

Fulvestrant (L)
Howell A, et al Post adjuvant TAM > 12 6.8 vs 8.3
Vs NA
(2004) months HR = 1.18
TAM

Robertson J, et al 16.6* vs 13.8

De novo MBC
(2017) HR = 0.79
Fulvatrant (H)
Vs NA
ANA
22.3 vs 13.8
No visceral met
HR = 0.59
 After nearly runout of
treatment option
After first line
3
1 2
Before initiate Px

Better partner than

AI ?
 First line CDK4/6 plus hormonal therapy

Ribociclib
Palbociclib Abemaciclib

Update MONALEESA-3
Trial PALOMA -2 MONALEESA - 2 MONALEESA -7 ASCO2021 (subgroup 1st MONARCH - 3
Subgroup 1st line line)

With Letrozole Letrozole AI or TAM Fulvestrant Fulvestrant Letrozole

27.6 vs 14.5 25.3 vs 16 23.8 vs 13 NR vs 18.3 28.1 vs 14.7

PFS
HR = 0.56 HR = 0.56 HR = 0.55 HR = 0.577 HR = 0.54
20
NR vs 29.7 NR vs 51.8 NR vs 45.1
OS Not yet report NR vs 33 HR = 0.712 HR = 0.640 HR = 0.7 Not yet report
P=0.00973 (0.464 - 0.883) (0.479-1.021)

ORR (%) 55.3 vs 44.4 52.7 vs 37.1 40.9 vs 29.7 NR 59 vs 44

Slamon D, et al. NEJM 2020.
 First line CDK4/6 plus hormonal therapy

Ribociclib
Palbociclib Abemaciclib

Update MONALEESA-3
Trial PALOMA -2 MONALEESA - 2 MONALEESA -7 ASCO2021 (subgroup 1st MONARCH - 3
Subgroup 1st line line)

With Letrozole Letrozole AI or TAM Fulvestrant Fulvestrant Letrozole

27.6 vs 14.5 25.3 vs 16 23.8 vs 13 32.2 vs 19.2 NR vs 18.3 28.1 vs 14.7

PFS
HR = 0.56 HR = 0.56 HR = 0.55 HR = 0.55 HR = 0.577 HR = 0.54
22
NR vs 29.7 NR vs 51.8 NR vs 45.1
OS Not yet report NR vs 33 HR = 0.712 HR = 0.640 HR = 0.7 Not yet report
P=0.00973 (0.464 - 0.883) (0.479-1.021)

ORR (%) 55.3 vs 44.4 52.7 vs 37.1 40.9 vs 29.7 NR 59 vs 44

 After nearly runout of
treatment option
After first line
3
1 2
Before initiate Px

Any predictive bio-

markers?
Which partner ?
 After nearly runout of
treatment option
After first line
3
1 2
Before initiate Px

Which one should you

test ?
Blood vs Tissue
Should we done earlier than this ?
 After nearly runout of
treatment option
After first line
3
1 2
Before initiate Px