Management of ER-Positive Postmenopausal Early Breast
Cancer
Current Hormonal Therapy Strategies for ER-Positive
Postmenopausal Breast Cancer
33
Adjuvant hormone therapy Adjuvant hormone therapy
(B) Postmenopausal(B) Postmenopausal
GNRH agonistsGNRH agonists
Breastcarcinoma
Breastcarcinoma
AntiestrogenAntiestrogen
Ovary
LHFSHLH
FSH
AntiestrogenAntiestrogen
(A) Premenopausal(A) Premenopausal
AdrenalAdrenalEstrogenEstrogen EstrogenEstrogen
AndrostenedioneAndrostenedione
AromataseinhibitorAromataseinhibitor
PeripheralaromatizationPeripheralaromatization
Adapted with permission from Tellez C, et al. Surg Oncol Clin North Am. 1995;4:751-777.
GNRH = Gonadotropin-releasing hormone; LH = Luteinizing hormone; FSH = Follicle-stimulating hormone.
clinicaloptions.com/oncology
Management of ER+ Postmenopausal Early Breast Cancer
clinicaloptions.com/oncology
Management of ER+ Postmenopausal Early Breast Cancer
Androstenedione
Steroidal Inactivators Androgen Substrate
OCH2
O
Exemestane
O
O
Nonsteroidal Inhibitors
CH3
CH3
CH3
CH3NC CN
AnastrozoleLetrozoleN
NC CNN
NNNN
Third-Generation Aromatase Inhibitors/Inactivators
Selective inhibitorsSelective inhibitors
Nonselective Nonselective inhibitorsinhibitorsMultiple steps involving P-450 enzymes and production of steroid Multiple steps involving P-450 enzymes and production of steroid
intermediatesintermediates
Cholesterol
Cortisol AndrostenedioneAldosterone
Testosterone
Estrone Estradiol
Federman, DD. The adrenal. Scientific American Medicine. Dale DC, Federman DD, eds. Section 3. Federman, DD. The adrenal. Scientific American Medicine. Dale DC, Federman DD, eds. Section 3. Subsection IV. ©1997 Scientific American Inc. All rights reserved.Subsection IV. ©1997 Scientific American Inc. All rights reserved.
Selective vs Nonselective Aromatase Inhibition
clinicaloptions.com/oncology
Management of ER+ Postmenopausal Early Breast Cancer
Recruitment: July 1996 - March 2000
Median follow-up: 100 months
84% hormone receptor positive
61% node negative
Anastrozole 1 mg/day + Tamoxifen 20 mg/day(n = 3215)
Tamoxifen20 mg/day (n = 3116)
Surgery ±RT ±
Chemotherapy
Anastrozole1 mg/day (n = 3125)
5-yrinterim analysis
Discontinued early
ATAC Trialists' Group. Lancet. 2004. Published online, December 8, 2004.
10-yranalysis planned
Postmenopausalwomen with
invasivebreast cancer
(N = 9366)
ATAC Trial
Pat
ien
ts (
%)
30
25
20
15
10
5
0
26182598
25412516
24532400
23612306
22782196
21592075
19951896
18011711
14921396
608547
At risk:AnastrozoleTamoxifen
13.9
16.4
25.8
29.9
0 1 2 3 4 5 6 7 8 9
30
25
20
15
10
5
0
TamoxifenAnastrozole
Follow-up Time (Yrs)
2.5 4.1
Reprinted from The Lancet Oncology, 2008;9:45-53, Forbes JF, et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Copyright (2008), with permission from Elsevier.
DFS: Hormone Receptor–Positive Patients
HR 95% CI
P Value
Hormone Receptor-Positive 0.85 (0.76-
0.94) .003
Absolute difference
7.8
9.1 13.2
15.6
Absolute difference 1.3 2.4
Pat
ien
ts (
%)
30
25
20
15
10
5
0
26182598
25512533
24702440
23932363
23202263
22012151
20421982
18541809
15361484
636591
At risk:AnastrozoleTamoxifen
0 1 2 3 4 5 6 7 8 9
30
25
20
15
10
5
0
Tamoxifen Anastrozole
Follow-up Time (Yrs)
Reprinted from The Lancet Oncology, 2008;9:45-53, Forbes JF, et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Copyright (2008), with permission from Elsevier.
HR 95%CI
P Value
Hormone Receptor-Positive 0.84 (0.72-
0.97) .022
Time to Distant Recurrence: Hormone Receptor–Positive Patients
ATAC: Endpoints HR+ Patients
Disease Free Survival
Time to Recurrence
Contralateral Br Ca
Time to Distant Recurrence
Death After Recurrence
Death: All Causes
FavorsAnastrozole
FavorsTamoxifen
Hazard Ratio(95%CI)
P Value
0.85 (0.76-0.94) 0.003
0.76 (0.67-0.87) 0.0001
0.60 (0.42-0.85) 0.004
0.84 (0.72-0.97) 0.022
0.90 (0.75-1.07) 0.2
0.97 (0.86-1.11) 0.7
0.2 0.4 0.6 0.8 1.0 1.2 1.5 2.0
Hazard ratio (A/T) and 95% CI
Forbes JF, et al. SABCS 2007. Abstract 41. Permission from author to print.
Significant long-term carryover effect for anastrozole
– Absolute difference in recurrence increased from 2.8% after 5 years to 4.8% after 9 years
– HR of anastrozole vs tamoxifen for Years 5-9: 0.75 (P = .01)
9-Yr Follow-up, %
Anastrozole Tamoxifen
Recurrence 17.0 21.8
HR: 0.76; P = .0001
Distant Recurrence 13.2 15.6
HR: 0.84; P = .022
Contralateral Breast Cancer 2.5 4.2
HR: 0.60; P = .004
DFS HR: 0.85; P = .003
Death After Recurrence HR: 0.90; P = .20
Forbes JF, et al. SABCS 2007. Abstract 41.
ATAC: Efficacy of Anastrozole vs Tamoxifen in HR+ Population
Tamoxifen
Letrozole
Tamoxifen Letrozole
Letrozole Tamoxifen
RANDOMIZE
0 2 5
YEARS
A
B
C
D
2-arm option3/98 - 3/001835 patients
4-arm option9/99 - 5/036193 patients
BIG 1-98: Study Design
T
0
20
40
60
80
100
0 1 2 3 4 5
Aliv
e an
d D
isea
se F
ree
(%)
Years From Randomization
97.797.6
LetTam
95.193.4
90.589.0
86.884.6
84.081.4
N HR (95% CI) P Value
8010 0.81 (0.70-0.93) .003
No. at Risk
38923896
29642926
12611238
892866
40034007
567544
Thurlimann B, et al. N Engl J Med. 2005;353:2747-2757. Copyright @ 2005 Massachusetts Medical Society. All rights reserved.
LetTam
Letrozole vs Tamoxifen: DFS
Years from RandomizationThurlimann B, et al. N Engl J Med. 2005;353:2747-2757. Copyright @ 2005 Massachusetts Medical Society. All rights reserved.
0 2 3 4 510
10
5
15
20
Fai
lure
(%
)
Letrozole
Tamoxifen
13.6
10.2
8.1
6.2
5-year difference (Letrozole-Tamoxifen): -3.4% (SE: 1.2%)Cumulative incidence: P = .0002
Cumulative Incidence: Breast Cancer Relapse
Year
BIG 1-98(BIG FEMTA)
TEAM EXE
ATAC
Tamoxifen
Anastrozole
Letrozole
Exemestane
Ongoing First-Generation Aromatase Inhibitor Adjuvant Trials
Exemestane(5162*)
Tamoxifen(5294*)
Tamoxifen(N = 4724)
Posttherapyfollow-up
2-3 years 2-3 years
5-yr total durationof endocrine therapy
Start of study
*Total women-years.
Postmenopausalwomen withcompletely
resected ER-positive or unknown statusearly-stage breast
cancer
Intergroup Exemestane Study: Trial Design
Intent-to-treat ER+/Unknown
Reprinted from The Lancet Oncology, 2006;7:991-996, Jonat W, et al. Effectiveness of switching from adjuvant tamoxifen to anastrozole in postmenopausal women with hormone-sensitive early-stage breast cancer: a meta-analysis. Copyright (2008), with permission from Elsevier.
Year
Abs diff, %(95% CI)
2.5 5.0
3.2(1.6-4.9)
3.4 (0.1-6.8)
2.5 5.0
3.4(1.8-5.1)
3.5(0.1-6.9)
End
oftreatm
ent
End
oftreatm
ent
HR: 0.75 (95% CI: 0.65-0.87)Log rank test: P = .0001
E = 339/2296
T = 438/2306
HR: 0.76 (95% CI: 0.66-0.88)Log rank test: P = .0001
E = 354/2352
T = 454/2372
Intent to treat ER+/Unknown
0102030405060708090
100
0 1 2 3 4 5
DF
S (
%)
0102030405060708090
100
0 1 2 3 4 5D
FS
(%
)
Exemestane After Tamoxifen: DFS
Time Since Randomization (Yrs) Time Since Randomization (Yrs)
End
oftreatm
ent
Year
Abs diff, % (95% CI)
2.5 5.0
0.8(-0.4 to 1.9)
1.2(-1.5 to 3.9)
2.5 5.0
0.7(-0.4 to 1.9)
1.6 (-1.2 to 4.3)
Reprinted from The Lancet Oncology, 2006;7:991-996, Jonat W, et al. Effectiveness of switching from adjuvant tamoxifen to anastrozole in postmenopausal women with hormone-sensitive early-stage breast cancer: a meta-analysis. Copyright (2008), with permission from Elsevier.
End
oftreatm
ent
HR: 0.83 (95% CI: 0.69-1.00)Log-rank test: P = .05
E = 210/2296
T = 251/2306
HR: 0.85 (95% CI: 0.71-1.02)Log-rank test: P =.08
E = 222/2352
T = 261/2372
Intent-to-treat ER+/Unknown
0102030405060708090
100
0 1 2 3 4 5Time Since Randomization (Yrs)
Wo
men
Ali
ve (
%)
0102030405060708090
100
0 1 2 3 4 5Time Since Randomization (Yrs)
Wo
men
Ali
ve (
%)
Exemestane After Tamoxifen: OS
ARNO 952 years of previous
tamoxifen (N = 979)
Jonat W, et al. Lancet Oncol. 2006;7:991-996.
Tamoxifen(n = 490)
Anastrozole (n = 489)
Year 5
ABCSG 82 years of previous
tamoxifen (N = 2579)
Tamoxifen(n = 1282)
Anastrozole (n = 1297)
ITA2-3 years of previous
tamoxifen (N = 448)
Tamoxifen 2-3 years(n = 225)
Anastrozole 2-3 years(n = 223)
Meta-analysis of Anastrozole Sequencing Studies
Time to DFS Event (Yrs)
2009 1522 1161 792 509 256 99 91997 1492 1109 764 460 241 78 9
Anastrozole
Tamoxifen
Reprinted from The Lancet Oncology, 2006;7:991-996, Jonat W, et al. Effectiveness of switching from adjuvant tamoxifen to anastrozole in postmenopausal women with hormone-sensitive early-stage breast cancer: a meta-analysis. Copyright (2008), with permission from Elsevier.
AnastrozoleTamoxifen
At risk:
0 1 2 4 5 6 70
60
70
80
90
100
Eve
nt
Fre
e (%
)
HR: 0.59 (95% CI: 0.48-0.74)
P < .0001
3 8
DFS: Anastrozole vs Tamoxifen (ITT Population)
0.2 0.4 0.6 0.8 1.0
ARNO 95
ITA
Meta-analysis
ABCSG 8
1.2 1.4 1.6
.726
.026
.094
.038
P value
2579
979
448
4006
Patients
0.93
0.48
0.50
0.71
HR
Favors anastrozole Favors tamoxifen
Hazard ratios and 95% confidence intervalsReprinted from The Lancet Oncology, 2006;7:991-996, Jonat W, et al. Effectiveness of switching from adjuvant tamoxifen to anastrozole in postmenopausal women with hormone-sensitive early-stage breast cancer: a meta-analysis. Copyright (2008), with permission from Elsevier.
OS: Anastrozole vs Tamoxifen (ITT Population)
Tamoxifen
Letrozole 2.5 mg daily (n = 2575)
Placebo(n = 2582)
5 years of early adjuvant 5 years of extended adjuvant
Node negative: n = 2581Node positive: n = 2370
30 months of follow-up
Extended Adjuvant TherapyMA.17: Trial Design
DFS* Distant* DFS
OS
Node-Negative Patients
Node-PositivePatients
HR: 0.61*(0.45-0.84)
HR: 0.45*(0.27-0.73)
HR: 0.63(0.31-1.27)
HR: 0.53*(0.36-0.78)
HR: 1.52(0.76-3.06)
HR: 0.61*(0.38-0.98)
*Statistically significant benefit of letrozole.
Goss PE, et al. J Natl Cancer Inst. 2005;17:1262-1271.
Extended Adjuvant Therapy:Letrozole After 5 Years of Tamoxifen
A similar reduction in local recurrences, new primaries, and distant recurrences occurred in node-positive and node-negative patients
Placebo (n = 2594)
5 years5 years
Letrozole (n = 1655)
1998 2003 Unblinding 2005
Letrozole (n = 2457)
No Letrozole (n = 613)
30 months 54 (16-86) monthsMedian follow-up
Goss PE, et al. SABCS 2005. Abstract 16.
Letrozole After Unblinding of MA.17
Tamoxifen(N = 5187)
Letrozole (n= 2593)
Goss PE, et al. SABCS 2005. Abstract 16.
DFS
Distant DFSOS
Contralateral breast cancer
HR
0.310.28
0.53
0.23
0
0.1
0.2
0.3
0.4
0.5
0.6
PLAC-LET to PLAC
P < .0001P < .002
P < .05
P < .012
Significant Advantage for PLAC-LET in Efficacy Outcomes
BIG 1-98(BIG FEMTA)
IES Trial
ITA
NSABP B33
Tamoxifen
Anastrozole
Placebo
Letrozole
Exemestane
MA-17
Ongoing First-Generation Aromatase Inhibitor Adjuvant Trials
Summary
Aromatase inhibitors offer a modest but significant benefit over tamoxifen in both the metastatic and adjuvant settings
In the adjuvant setting, it remains unclear whether upfront aromatase inhibitor therapy is superior to sequencing approach
High-risk premenopausal patients should receive an aromatase inhibitor as part of their adjuvant therapy (after 2 years, 5 years, or when off tamoxifen)
Endocrine Therapy for Metastatic Breast Cancer
clinicaloptions.com/oncology
Management of ER+ Postmenopausal Early Breast Cancer
Initial Treatment of HR-Positive Advanced Breast Cancer AIs are the current standard of care for initial treatment of postmenopausal women with
HR-positive advanced breast cancer
AIs have demonstrated improved efficacy compared with tamoxifen
– TTP, anastrozole vs tamoxifen: 10.7 vs 6.4 mos[6]
– TTP, letrozole vs tamoxifen: 9.4 vs 6.0 mos[5]
– PFS, exemestane vs tamoxifen: 9.9 vs 5.8 mos[7]
Fulvestrant has demonstrated improved efficacy compared with anastrozole
– TTP, fulvestrant vs anastrozole: 23.4 vs 13.1 mos [8]
– Fulvestrant has demonstrated similar efficacy compared with tamoxifen [9]
– Combination fulvestrant and anastrozole was more efficacious than anastrozole alone [10]
6. Bonneterre J, et al. Cancer. 2001;92:2247-2258. 5. Mouridsen H, et al. J Clin Oncol. 2003;21:2101-2109. 7. Paridaens RJ, et al. J Clin Oncol. 2008;26:4883-4890. 8. Robertson FJ, et al. Breast Cancer Res Treat. 2012;136:503-511. 9. Howell A, et al. J Clin Oncol. 2004;22:1605-1613. 10. Mehta RS, et al. N Engl J Med 2012;367:435-444.
First-line Letrozole vs Tamoxifen, Then Crossover
Median OSLetrozole: 34 mosTamoxifen: 30 mos
Time to Crossover Letrozole: 17 mos Tamoxifen: 14 mos
Mouridsen H, et al. J Clin Oncol. 2003;21:2101-2109.
P = .53 (long-rank test)
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
00 6 12 18 24 30 36 42 48 54 60
Mos
Pro
po
rtio
n A
live
Letrozole 1st Tamoxifen 1st
In the CONFIRM trial, 500 mg of monthly fulvestrant was superior to 250 mg for which survival endpoints?
A. PFS, but not OS
B. Both PFS and OS
C. Neither PFS nor OS
In the CONFIRM trial, 500 mg of monthly fulvestrant was superior to 250 mg for which survival endpoints?
A. PFS, but not OS
B. Both PFS and OS
C. Neither PFS nor OS
CONFIRM: Fulvestrant 500 mg vs 250 mg in Postmenopausal Women With ER+ MBC
Fulvestrant 250 mg*(n = 374)
Fulvestrant 500 mg†
(n = 362)
Postmenopausal women
with ER-positive advanced
breast cancer (N = 736)
*Fulvestrant 250 mg: 1 injection of fulvestrant 250 mg IM + 1 placebo injection on Day 0; 2 placebo injections on Day 14; 1 injection of fulvestrant 250 IM + 1 placebo injection on Day 28, then every 28 days thereafter.†Fulvestrant 500 mg: 2 injections of fulvestrant 250 mg IM on Days 0, 14, 28, then every 28 days thereafter.
DiLeo A, et al. SABCS 2012. Abstract S1-4.
CONFIRM: Effect of Fulvestrant 500 mg vs 250 mg on Survival in Postmenopausal Women Baseline characteristics appeared well balanced between treatment arms
– Subsequent therapies were well balanced between arms, with approximately 60% of patients receiving subsequent chemotherapy and approximately one third receiving other hormonal therapy
OutcomeTiming of Analysis
Fulvestrant500 mg
Fulvestrant250 mg HR (95% CI)
Median PFS First* 6.5 mos 5.5 mos 0.80‡ (0.68-0.94)
Median OS First* 25.1 mos 22.8 mos 0.84§ (0.69-1.03)
Median OS Final† 26.4 mos 22.3 mos 0.81¶ (0.69-0.96)*First analysis was performed at 50% maturity.†Final analysis was performed at 75% maturity. ‡ P = .006 §P = .001 ¶P = .016
DiLeo A, et al. SABCS 2012. Abstract S1-4.
FIRST Study Design
Robertson JF, et al. Clin Oncol. 2009;27:4530-4535.
Endpoints at primary data cutoff
Primary endpoint
Clinical benefit rate
Secondary endpoints
ORR
TTP
Duration of response
Duration of clinical benefit
Safety
Exploratory endpoint
Best response to subsequent therapy
Open-label first-line ER+ postmenopausal patients with advanced breast cancer
(target, N = 200; actual, N = 205)
Fulvestrant 500 mg IMon Days 0, 14, 28, and
every 28 days thereafter
Anastrozole 1 mg/day PO
Progression
Follow-up
Progression
Follow-up
0
0.2
0.4
0.6
0.8
1.0
0 6 12 18 24
Mos
30 36 42 48
Fulvestrant 500 mgAnastrozole 1 mg
Pro
po
rtio
n o
f P
atie
nts
Aliv
ean
d P
rog
ress
ion
Fre
e
HR: 0.66 (95% CI: 0.47-0.92;P = .01)
Pts at Risk, nFulvestrant 500 mgAnastrozole 1 mg
102103
7469
6555
5239
4530
3421
208
62
00
Robertson JF, et al. Breast Cancer Res Treat. 2012;136:503-511.
FIRST: TTP at Follow-up Analysis
Postmenopausal women with hormone receptor–
positive MBC(N = 707)
Anastrozole 1 mg/day PO +Fulvestrant 500 mg on Day 1,
250 mg on Days 14 and 28, 250 mg every 28 days thereafter
(n = 355)
Anastrozole 1 mg/day PO(n = 352)
Treatment until disease progression
Stratified by previous adjuvant tamoxifen
Women with progression
encouraged to cross over to receive
fulvestrant
Mehta RS, et al. N Engl J Med. 2012;367:435-444.
SWOG S0226: Study Design
Primary endpoint: PFS Secondary endpoints: OS, safety
SWOG S0226: PFS and OS Overall and by Previous Adjuvant TamoxifenEndpoint Anastrozole
+ FulvestrantAnastrozole HR (95% CI) P
Value
Median PFS (n = 694), mos
15.0 13.5 0.80(0.68-0.94)
.007
No previous adjuvant tamoxifen (n = 414)
17.0 12.6 0.74(0.59-0.92)
.0055
Previous adjuvant tamoxifen (n = 280)
13.5 14.1 0.89(0.69-1.15)
.37
Median OS (n = 694), mos
47.7 41.3 0.81(0.65-1.00)
.049
No previous adjuvant tamoxifen (n = 414)
47.7 39.7 0.74(0.56-0.98)
.0362
Previous adjuvant tamoxifen (n = 280)
49.6 44.5 0.91 (0.65-1.28)
.59
Mehta RS, et al. N Engl J Med. 2012;367:435-444.
Finn RS, et al. SABCS 2012. Abstract S1-6.
Aromatase Inhibitor + CDK4/6 Inhibitor Improves PFS in ER+ MBC
0
0.2
0.4
0.6
0.8
1.0
0 6 1210 14Mos
16 20 22 28
PD 991 + LET (n = 84)21 (25)
26.1(12.7-26.1)
PF
S P
rob
abili
ty
Pts at Risk, nPD 991 + LETLET
8481
7557
6038
5329
4322
3517
2511
31
11
24 261882 4
0.3
0.5
0.7
0.9
0.1
LET (n = 81)40 (49)
7.5(5.6-12.6)
186
155
144
93
53
Events, n (%)Median PFS, mos(95% CI)HR(95% CI)P value
0.37(0.21-0.63)
< .001
EFFECT: Fulvestrant vs Exemestane After Progression of Nonsteroidal AI
MosPts at Risk, nFulvestrantExemestane
3.73.7Median, mos
HR: 0.963 (95% CI: 0.819-1.133; P = .6531)
Cox analysis, P = .7021
ExemestaneFulvestrant
FulvestrantExemestane
0 3 6 9 12 15 18 21 24 270.0
0.2
0.4
0.6
0.8
1.0
351 195 96 50 25 12 4 2
342 190 98 41 21 12 8 6
0
1
0
0Chia S, et al. J Clin Oncol. 2008;26:1664-1670.
Patients with which site of metastatic disease had the longest PFS with exemestane + everolimus vs exemestane in the BOLERO-2 trial?A. Bone only
B. Liver only
C. Lung only
D. Any visceral disease
E. No visceral disease
Patients with which site of metastatic disease had the longest PFS with exemestane + everolimus vs exemestane in the BOLERO-2 trial?A. Bone only
B. Liver only
C. Lung only
D. Any visceral disease
E. No visceral disease
Reprinted by permission from the American Association for Cancer Research: Johnston SR. Clin Cancer Res. 2005;11:889s-899s.
ER target gene transcription
SOS
P PP P
PI3-K
akt
PP
RASRAF
MEK
MAPKp90RSK
ER
Pp160
BasaltranscriptionmachineryCBPERER
PPP
ERE
Plasmamembrane
Cytoplasm
Nucleus
E2
SERD
AI T
IGF1R
EGFR/HER2
Increased signalingthrough PI3-K pathway
Increased signaling throughEGFR and/or IGF1-R
VEGFR
Mechanisms of Hormone Resistance
BOLERO-2: Everolimus + Exemestane Improves PFS in HR+ MBC
Baselga J, et al. N Engl J Med. 2012;366:520-529.
0 6 12 18 24 30 36 42 48 54 60 66 72 78
Wks
Pro
bab
ility
of
Eve
nt
(%) Everolimus + exemestane
(median PFS: 10.6 mos)
Placebo + exemestane(median PFS: 4.1 mos)
HR: 0.36 (95% CI: 0.27-0.47;log-rank P < .001)
Patients at Risk, n
Everolimus
Placebo
485
239
385
168
281
94
201
55
132
33
102
20
67
11
43
11
28
6
18
3
9
3
3
1
2
0
0
0
100908070605040302010
0
Central Assessment
BOLERO-2: Final PFS Analysis (18-Mo Follow-up)PFS, Mos EVE + EXE PBO + EXE HR (95% CI) P Value
Local review 7.8 3.2 0.45(0.38-0.54)
< .0001
Central review 11.0 4.1 0.38(0.31-0.48)
< .0001
With visceral mets 6.83 2.76 0.47(0.37-0.60)
--
Without visceral mets 9.86 4.21 0.41(0.31-0.55)
--
Bone-only mets 12.88 5.29 0.33(0.21-0.53)
--
Progression after neo/adj therapy
11.50 4.07 0.39(0.25-0.62)
--
OS data still not mature (HR: 0.77; 95% CI: 0.57-1.04)
Most common grade 3/4 AEs were stomatitis (8%), hyperglycemia (5%), fatigue (4%)
Piccart, M, et al. SABCS 2012. Abstract P6-04-02.
Case
A 68-yr-old woman presents with a T4N2 left breast mass with associated contraction and fibrosis that had been developing over 3-4 yrs
Breast biopsy shows ER+/PgR+, HER2- IDC, grade 2
Staging evaluation shows bone metastases and multiple pulmonary nodules
The patient has mild DOE but no bone pain
clinicaloptions.com/oncology
Management of ER+ Postmenopausal Early Breast Cancer
An IV bisphosphonate or SC denosumab is recommended for this patient, but which of the following endocrine therapies is NOT recommended?
A. Fulvestrant 500 mg
B. Letrozole
C. Exemestane + everolimus
D. Fulvestrant + a nonsteroidal AI
clinicaloptions.com/oncology
Management of ER+ Postmenopausal Early Breast Cancer
An IV bisphosphonate or SC denosumab is recommended for this patient, but which of the following endocrine therapies is NOT recommended?
A. Fulvestrant 500 mg
B. Letrozole
C. Exemestane + everolimus
D. Fulvestrant + a nonsteroidal AI
clinicaloptions.com/oncology
Management of ER+ Postmenopausal Early Breast Cancer
Endocrine Therapy Sequencing in MBC: Which Order Is Best? AI or fulvestrant are most effective first-line single agents;
fulvestrant ± AI reasonable choice for endocrine therapy–naive patients with MBC
Continue endocrine therapies until resistance
mTOR inhibition with everolimus + exemestane is best second-line therapy after progression on nonsteroidal AI
After everolimus, back to anti-ER therapy alone or enhanced blockade of PI3K pathway
Addition of CDK4/6 inhibitor to first-line letrozole may become a new SOC; phase III trial under way