1. Phase III SOLE: Continuous vs Intermittent Extended Letrozole After Adjuvant Endocrine Therapy in Early HR+ Breast Cancer
CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois
*Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals
HR, hormone receptor.
This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

2. Continuous vs Intermittent Letrozole After Endocrine Tx in Breast Cancer (SOLE): Background
Extended adjuvant endocrine therapy with letrozole recommended after tamoxifen for postmenopausal women with HR-positive breast cancer[1]
Magnitude of benefit limited in pts who received an AI during first 5 yrs[2]
Extended therapy brings concerns about development of resistance to antihormonal therapy or spontaneous tumor growth in an estrogen-free environment[3]
SOLE: randomized phase III trial evaluating use of intermittent letrozole as option to prolong sensitivity to endocrine treatment[4]
Preclinical evidence for enhanced antitumor activity with a minimal concentration of estrogen achieved through intermittent AI therapy[5]
AI, aromatase inhibitor; HR, hormone receptor; Tx, treatment.
1. Goss PE, et al. N Engl J Med. 2003;349: Mamounas T, et al. SABCS Abstract S Song RX, et al. J Natl Cancer Inst. 2001;93: Colleoni M, et al. ASCO Abstract Sabnis GJ, et al. Cancer Res. 2008;68:
Slide credit: clinicaloptions.com

3. SOLE: Study Design * * * * * 0 6 12 18 24 30 36 42 48 54 60 mos
Stratified by prior adjuvant endocrine therapy (AI, SERM, or both)
Continuous letrozole for 5 yrs (n = 2426)
Postmenopausal women with clinically disease free HR+ lymph node-positive early BC who have completed 4-6 yrs of adjuvant endocrine therapy
(N = 4851)
Intermittent letrozole over 5 yrs (n = 2425)
AI, aromatase inhibitor; BC, breast cancer; BCFI, breast cancer–free interval; DRFI, distant recurrence-free interval; HR, hormone receptor; QoL, quality of life; SERM, selective estrogen receptor modulator.
mos
Endpoints
Primary: DFS
Secondary: BCFI, DRFI, OS * * * * *
QoL substudy timepoints completed by 955 pts
Slide credit: clinicaloptions.com
Colleoni M, et al. ASCO Abstract 503.

4. SOLE: Pt Characteristics
All Pts
(N = 4851)
Continuous Let
(n = 2426)
Intermittent Let
(n = 2425)
Median age at randomization, yrs 60
Tumor > 2 cm, % 52
Grade 3 disease, % 24 25 23
> 3 positive lymph nodes, % 33
HER2+, % 17 18 15
Prior AI only, % 43
Median duration of prior endocrine therapy, yrs 5
AI, aromatase inhibitor; Let, letrozole
Slide credit: clinicaloptions.com
Colleoni M, et al. ASCO Abstract 503.

5. SOLE: DFS (Primary Endpoint)
Patients, n
HR (95% CI)
5-Yr DFS, %
Intermittent
Continuous
Intermittent
Continuous
5-yr DFS 87.5%
100
All Pts
2425
2426
85.8
87.5
Prior Endocrine Therapy SERM(s) only
Both SERM(s) and AI(s)
AL(s) only
1008
1014
87.3
85.3
85.6
90.9
87.5
85.9 80
85.8%
Continuous letrozole Intermittent letrozole 60
.25 .5
.75 1
1.5 2
Alive and Disease Free (%)
Favors Intermittent Let
Favors Continuous Let 40
DFS Event, %
Continuous Let
(n = 2426)
Intermittent Let
(n = 2425)
DFS event
13.1
14.3
BC event as first site
8.9
8.7
Second malignancy (nonbreast)
3.1
3.9
Death without cancer event
0.9
1.4
Death, incomplete information
0.3 N
Events
HR (95% CI) ( )
P Value .31 20
AI, aromatase inhibitor; BC, breast cancer; DFS, disease-free survival; Let, letrozole; SERM, selective estrogen receptor modulator.
Continuous
Intermittent 1 2 3 4 5 6
Yrs Since Randomization
Median follow-up: 60 mos
Slide credit: clinicaloptions.com
Colleoni M, et al. ASCO Abstract 503. Reproduced with permission.

6. SOLE: Breast Cancer–Free Interval and Distant Recurrence-Free Interval
5-yr BCFI 91.2%
5-yr DCFI 93.2%
100
100
90.9%
92.5% 80 80
Continuous letrozole Intermittent letrozole
Continuous letrozole Intermittent letrozole 60 60
Percent Without Breast Cancer
Percent Without Distant Recurrence 40 40 N
Events
HR (95% CI) .98 ( )
P Value .84 N
Events
HR (95% CI) .88 ( )
P Value .25 20
BCFI, breast cancer–free interval; DRFI, distant recurrence-free interval. 20
Continuous
Intermittent
Continuous
Intermittent 1 2 3 4 5 6 1 2 3 4 5 6
Yrs Since Randomization
Yrs Since Randomization
Slide credit: clinicaloptions.com
Colleoni M, et al. ASCO Abstract 503. Reproduced with permission.

7. Yrs Since Randomization
SOLE: OS
5-yr OS 94.3%
Patients, n
HR (95% CI)
5-Yr OS, %
100
Intermittent
Continuous
Intermittent
Continuous
93.7% 80
All Pts
2425
2426
94.3
93.7
Continuous letrozole Intermittent letrozole
Prior Endocrine Therapy SERM(s) only
Both SERM(s) and AI(s) 60
435
93.8
94.2
94.7
96.4
94.1
92.2
Percent Alive
977 40
AL(s) only
1014
1008 N
Events
HR (95% CI) ( )
P Value .16 20
AI, aromatase inhibitor; SERM, selective estrogen receptor modulator.
.25 .5
.75 1
1.5 2
Continuous
Intermittent
Favors Intermittent
Favors Continuous 1 2 3 4 5 6
Yrs Since Randomization
Median follow-up: 60 mos
Slide credit: clinicaloptions.com
Colleoni M, et al. ASCO Abstract 503. Reproduced with permission.

8. SOLE: Treatment Adherence
Time to Permanent Discontinuation of Letrozole 2
98%, 97%, 97%, 91% resumed after planned interruption
Intermittent Letrozole:
% of Days on Letrozole (3-Mo Intervals)
1.0
0.8
0.6
0.4
0.2
Mean Percentage of Days on Treatment 20 1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Quarter Since Randomization
100 80 60
Continuous letrozole Intermittent letrozole
Percent on Treatment 40
8% stopped for DFS event
24% stopped early, other reasons
39% completed 5 years
29% continue on treatment
DFS, disease-free survival. 20 1 2 3 4 5 6
Yrs Since Randomization
Slide credit: clinicaloptions.com
Colleoni M, et al. ASCO Abstract 503. Reproduced with permission.

9. SOLE: Safety Select AEs, % Continuous Let (n = 2411)
Intermittent Let (n = 2417)
Any Grade
Grade 3-5
Any grade 3-5 AE
34.5
36.2
Arthralgia
68.7
6.3
65.8
5.6
Hot flushes/flashes
54.3
2.9
52.9
2.4
Osteoporosis
46.9
0.7
47.5
1.1
Fatigue
44.9
41.5
2.0
Hypertension
43.8
21.4
44.6
24.2
Insomnia
43.2
42.0
2.2
Myalgia
37.1
36.1
Depression
34.1
2.5
Bone pain
28.7
27.3
1.9
Fractures
8.9
2.7
8.3
2.6
CNS cerebrovascular ischemia
1.7
1.2
1.4
1.0
Cardiac ischemia
1.5
0.9
1.8
0.8
CNS hemorrhage
0.5
0.3
0.6
0.4
AE, adverse event; CNS, central nervous system; Let, letrozole.
Slide credit: clinicaloptions.com
Colleoni M, et al. ASCO Abstract 503.

10. SOLE: Conclusions
Extended intermittent letrozole did not improve DFS vs continuous dosing in postmenopausal women with HR+ breast cancer
Trend toward differential effect seen depending on prior endocrine therapy (AI vs SERM)
No change in safety profile with intermittent vs continuous dosing
Study investigators suggest that this data could provide clinically relevant information for pts who could benefit from temporary treatment breaks during extended letrozole therapy
Translational studies ongoing with prospectively collected tissue samples
AI, aromatase inhibitor; DFS, disease-free survival; HR, hormone receptor; SERM, selective estrogen receptor modulator.
Slide credit: clinicaloptions.com
Colleoni M, et al. ASCO Abstract 503.

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