1) Everolimus combined with exemestane nearly tripled progression-free survival compared to placebo and exemestane for patients with hormone receptor-positive, HER2-negative advanced breast cancer previously treated with adjuvant aromatase inhibitors. 2) A subgroup analysis found everolimus and exemestane doubled progression-free survival compared to standard treatment as first-line therapy for advanced breast cancer after prior aromatase inhibitor treatment. 3) A real-world study found everolimus to be associated with significantly longer progression-free survival compared to fulvestrant among postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer refractory to aromatase inhibitors.

1. Tailoring Endocrine
therapies in ABC:
FUL vs EVE + EXE in
2nd line ET

2. Case
 Patient aged 58, no relevant co-morbidities,
menopause for the last five years
 Three years ago, right quadrantectomy and
axillary dissection for ductal infiltrating
carcinoma pT 2.2 cm, N+ 1/18, G2, ER+ 50%,
PgR+ 30%, HER2-negative, Ki-67 25%
 She received 4 TC  RT + anastrozole
 While on anastrozole, appearance of a breast
scar nodule

3. Case (continued)
 Exeresis of the breast scar nodule. Pathology:
local relapse from breast cancer, ER- and PgR-
negative, HER2-negative
 Treatment options:
 wait and see
 adjuvant chemotherapy
 adjuvant chemotherapy  endocrine therapy
 endocrine therapy

4. Indication
Fulvestrant is indicated for the treatment of HR+ MBC
in postmenopausal women with disease progression
following antiestrogen therapy.
Everolimus: postmenopausal women with advanced
hormone receptor-positive, HER2-negative breast
cancer (advanced HR+ BC) in combination with
exemestane after failure of treatment with letrozole
or anastrozole.
As a 2nd and later lines of therapy
after the failure of NSAIs

5. EVE + EXE Placebo + EXE

6. PFS
Study
population
EVE + EXE
(mos)
PLA + EXE
(mos)
Risk
reduction
(%)
ABC/MBC1 Overall
population
11.5 4.1 61%
• Recurrent LABC Neo/Adj Therapy 15.2 4.2 68%
• MBC2
Bone-Only 12.9 5.3 67%
Visceral 6.8 2.7 53%
The present subset analysis from BOLERO-2 demonstrated
that EVE+EXE as first-line therapy for advanced breast
cancer nearly tripled PFS in patients with HR+, HER2-
advanced breast cancer previously treated with (neo)adjuvant NSAIs.previously treated with (neo)adjuvant
NSAIs.
overall BOLERO-2 trial population, EVE+EXE more than doubled the median
PFS
Ref: 1. Beck J T. Breast Cancer Res Treat (2014) 143:459–467
2. Piccart M, et al. J Clin Oncol.2012;30.

7. BOLERO-2 subgroup analysis
 19 % of pts who received EVE+EXE as 1st-line
treatment for advanced breast cancer after NSAIs
 PFS= 11.5 mo vs 4.1 mo (tripled)
 EVE+EXE as 1st-line therapy for ABC nearly tripled
PFS in patients with HR+, HER2- advanced breast
cancer previously treated with (neo)adjuvant
NSAIs.
Beck J T. Breast Cancer Res Treat (2014)

8. CONFIRM: Fulvestrant 250 mg vs
Fulvestrant 500 mg
Phase III, Randomized, Double-blind, multicentric clinical trial
8
Di Leo A. J Clin Oncol. 2010 Oct 20;28(30):4594-600
86.3% of pts recurred or progressed during or after 1
prior ET.

9. 1/12/201
6
9
26.4
mos
22.3
mos
19% relative reduction in the risk of death and a 4.1-
month increase in median OS (Not statistically
significant)
OS
6.5 mos
5.4 mos
20%
Relative Risk
reduction
PFS

10. Summary of resistance in breast cancer
J. M. Dixon, “Endocrine Resistance in Breast Cancer,” New Journal of Science, vol.
2014, Article ID 390618, 27 pages, 2014.
IHC-4

11. J. Comp. Eff. Res. (2015) 4(4), 315–326
Aims:
Assessing real-world effectiveness of EVE vs FUL among
postmenopausal women with HR+/HER2- MBC after
progression on NSAI.

12. Pt Demographics
 A lower proportion of EVE patients had Bone
metastases (62 vs 77%; p = 0.002)
 However, a greater proportion of EVE pts had
liver metastases (35 vs 17%; p < 0.0001),
visceral metastases (60 vs 44%; p = 0.004) and
prior chemotherapy in the mBC setting (22 vs
13%; p = 0.021).

13. Results & conclusion:
 N = EVE (192) and FUL (156 )
 PFS = 9.1 mos for EVE vs 7.3 mos for FUL
 EVE was associated with significantly longer PFS
than FUL (HR: 0.71; p = 0.045)
Adjustments line of therapy and treatment groups:
PFS was significantly longer in pts who received
EVE in 2nd line, or 3rd and later lines than
patients who received FUL in the same lines.
EVE was associated with better PFS (9.1 vs 7.3; HR=0.71, p=0.045)
than FUL among NSAI-refractory postmenopausal HR+/HER2- MBC pts
Results suggested that pts who received EVE
have MORE AGGRESSIVE MBC, compared with pts
who received FUL.

14. In general, which initial antitumor treatment would
you recommend for a 68-year-old woman with ER+,
HER2-neg breast cancer who develops asymptomatic
bone and liver metastases 3.5 years after starting
adjuvant letrozole?
2%
5%
35%
8%
8%
40%
0% 10% 20% 30% 40% 50%
Other
Chemotherapy
Everolimus + exemestane
Exemestane
Tamoxifen
Fulvestrant
http://www.researchtopractice.com/SABCS15/Video

15. Conclusion: In 2nd line
FUL
 Acquired
Resistance
 Bone Metastases
 Any age
EVE + EXE
 Aggressive tumor –
Resistance within 1 yrs
 Bone as well as visceral
metastases
 Young patient (< 70 yrs)
 For > 70 yrs 5 mg