Sorry, you need to enable JavaScript to visit this website.

AROMASIN® (exemestane) Clinical Studies

14 CLINICAL STUDIES

14.1 Adjuvant Treatment in Early Breast Cancer

The Intergroup Exemestane Study 031 (IES) was a randomized, double-blind, multicenter, multinational study comparing exemestane (25 mg/day) vs. tamoxifen (20 or 30 mg/day) in postmenopausal women with early breast cancer. Patients who remained disease-free after receiving adjuvant tamoxifen therapy for 2 to 3 years were randomized to receive an additional 3 or 2 years of AROMASIN or tamoxifen to complete a total of 5 years of hormonal therapy.

The primary objective of the study was to determine whether, in terms of disease-free survival, it was more effective to switch to AROMASIN rather than continuing tamoxifen therapy for the remainder of five years. Disease-free survival was defined as the time from randomization to time of local or distant recurrence of breast cancer, contralateral invasive breast cancer, or death from any cause.

The secondary objectives were to compare the two regimens in terms of overall survival and long-term tolerability. Time to contralateral invasive breast cancer and distant recurrence-free survival were also evaluated.

A total of 4724 patients in the intent-to-treat (ITT) analysis were randomized to AROMASIN (exemestane tablets) 25 mg once daily (N = 2352) or to continue to receive tamoxifen once daily at the same dose received before randomization (N = 2372). Demographics and baseline tumor characteristics are presented in Table 5. Prior breast cancer therapy is summarized in Table 6.

Table 5. Demographic and Baseline Tumor Characteristics from the IES Study of Postmenopausal Women with Early Breast Cancer (ITT Population)
Parameter Exemestane
(N = 2352)
Tamoxifen
(N = 2372)
*
Results for receptor status include the results of the post-randomization testing of specimens from subjects for whom receptor status was unknown at randomization.
Only one subject in the exemestane group had unknown ER status and positive PgR status.
Age (years):
Median age (range) 63.0 (38.0 – 96.0) 63.0 (31.0 – 90.0)
Race, n (%):
Caucasian 2315 (98.4) 2333 (98.4)
Hispanic 13 (0.6) 13 (0.5)
Asian 10 (0.4) 9 (0.4)
Black 7 (0.3) 10 (0.4)
Other/not reported 7 (0.3) 7 (0.3)
Nodal status, n (%):
Negative 1217 (51.7) 1228 (51.8)
Positive 1051 (44.7) 1044 (44.0)
  1–3 Positive nodes 721 (30.7) 708 (29.8)
  4–9 Positive nodes 239 (10.2) 244 (10.3)
  >9 Positive nodes 88 (3.7) 86 (3.6)
  Not reported 3 (0.1) 6 (0.3)
Unknown or missing 84 (3.6) 100 (4.2)
Histologic type, n (%):
Infiltrating ductal 1777 (75.6) 1830 (77.2)
Infiltrating lobular 341 (14.5) 321 (13.5)
Other 231 (9.8) 213 (9.0)
Unknown or missing 3 (0.1) 8 (0.3)
Receptor status*, n (%):
ER and PgR Positive 1331 (56.6) 1319 (55.6)
ER Positive and PgR Negative/Unknown 677 (28.8) 692 (29.2)
ER Unknown and PgR Positive/Unknown 288 (12.2) 291 (12.3)
ER Negative and PgR Positive 6 (0.3) 7 (0.3)
ER Negative and PgR Negative/Unknown (none positive) 48 (2.0) 58 (2.4)
Missing 2 (0.1) 5 (0.2)
Tumor Size, n (%):
≤ 0.5 cm 58 (2.5) 46 (1.9)
> 0.5 – 1.0 cm 315 (13.4) 302 (12.7)
> 1.0 – 2 cm 1031 (43.8) 1033 (43.5)
> 2.0 – 5.0 cm 833 (35.4) 883 (37.2)
> 5.0 cm 62 (2.6) 59 (2.5)
Not reported 53 (2.3) 49 (2.1)
Tumor Grade, n (%):
G1 397 (16.9) 393 (16.6)
G2 977 (41.5) 1007 (42.5)
G3 454 (19.3) 428 (18.0)
G4 23 (1.0) 19 (0.8)
Unknown/Not Assessed/Not reported 501 (21.3) 525 (22.1)
Table 6. Prior Breast Cancer Therapy of Patients in the IES Study of Postmenopausal Women with Early Breast Cancer (ITT Population)
Parameter Exemestane
(N = 2352)
Tamoxifen
(N = 2372)
*
The 30 mg dose was used only in Denmark, where this dose was the standard of care.
Type of surgery, n (%):
Mastectomy 1232 (52.4) 1242 (52.4)
Breast-conserving 1116 (47.4) 1123 (47.3)
Unknown or missing 4 (0.2) 7 (0.3)
Radiotherapy to the breast, n (%):
Yes 1524 (64.8) 1523 (64.2)
No 824 (35.5) 843 (35.5)
Not reported 4 (0.2) 6 (0.3)
Prior therapy, n (%):
Chemotherapy 774 (32.9) 769 (32.4)
Hormone replacement therapy 567 (24.1) 561 (23.7)
Bisphosphonates 43 (1.8) 34 (1.4)
Duration of tamoxifen therapy at randomization (months):
Median (range) 28.5 (15.8 – 52.2) 28.4 (15.6 – 63.0)
Tamoxifen dose, n (%):
20 mg 2270 (96.5) 2287 (96.4)
30 mg* 78 (3.3) 75 (3.2)
Not reported 4 (0.2) 10 (0.4)

After a median duration of therapy of 27 months and with a median follow-up of 34.5 months, 520 events were reported, 213 in the AROMASIN group and 307 in the tamoxifen group (Table 7).

Table 7. Primary Endpoint Events (ITT Population)
Event First Events
N (%)
Exemestane
(N = 2352)
Tamoxifen
(N = 2372)
Loco-regional recurrence 34 (1.45) 45 (1.90)
Distant recurrence 126 (5.36) 183 (7.72)
Second primary – contralateral breast cancer 7 (0.30) 25 (1.05)
Death – breast cancer 1 (0.04) 6 (0.25)
Death – other reason 41 (1.74) 43 (1.81)
Death – missing/unknown 3 (0.13) 5 (0.21)
Ipsilateral breast cancer 1 (0.04) 0
Total number of events 213 (9.06) 307 (12.94)

Disease-free survival in the intent-to-treat population was statistically significantly improved [Hazard Ratio (HR) = 0.69, 95% CI: 0.58, 0.82, P = 0.00003, Table 8, Figure 1] in the AROMASIN arm compared to the tamoxifen arm. In the hormone receptor-positive subpopulation representing about 85% of the trial patients, disease-free survival was also statistically significantly improved (HR = 0.65, 95% CI: 0.53, 0.79, P = 0.00001) in the AROMASIN arm compared to the tamoxifen arm. Consistent results were observed in the subgroups of patients with node negative or positive disease, and patients who had or had not received prior chemotherapy.

An overall survival update at 119 months median follow-up showed no significant difference between the two groups, with 467 deaths (19.9%) occurring in the AROMASIN group and 510 deaths (21.5%) in the tamoxifen group.

Table 8. Efficacy Results from the IES Study in Postmenopausal Women with Early Breast Cancer
ITT Population Hazard Ratio
(95% CI)
p-value
(log-rank test)
*
Not adjusted for multiple testing.
Disease-free survival 0.69 (0.58–0.82) 0.00003
Time to contralateral breast cancer 0.32 (0.15–0.72) 0.00340
Distant recurrence-free survival 0.74 (0.62–0.90) 0.00207
Overall survival 0.91 (0.81–1.04) 0.16*
ER and/or PgR positive
Disease-free survival 0.65 (0.53–0.79) 0.00001
Time to contralateral breast cancer 0.22 (0.08–0.57) 0.00069
Distant recurrence-free survival 0.73 (0.59–0.90) 0.00367
Overall survival 0.89 (0.78–1.02) 0.09065*
Figure 1. Disease-Free Survival in the IES Study of Postmenopausal Women with Early Breast Cancer (ITT Population)
Figure 1

14.2 Treatment of Advanced Breast Cancer

Exemestane 25 mg administered once daily was evaluated in a randomized double-blind, multicenter, multinational comparative study and in two multicenter single-arm studies of postmenopausal women with advanced breast cancer who had disease progression after treatment with tamoxifen for metastatic disease or as adjuvant therapy. Some patients also have received prior cytotoxic therapy, either as adjuvant treatment or for metastatic disease.

The primary purpose of the three studies was evaluation of objective response rate (complete response [CR] and partial response [PR]). Time to tumor progression and overall survival were also assessed in the comparative trial. Response rates were assessed based on World Health Organization (WHO) criteria, and in the comparative study, were submitted to an external review committee that was blinded to patient treatment. In the comparative study, 769 patients were randomized to receive AROMASIN (exemestane tablets) 25 mg once daily (N = 366) or megestrol acetate 40 mg four times daily (N = 403). Demographics and baseline characteristics are presented in Table 9.

Table 9. Demographics and Baseline Characteristics from the Comparative Study of Postmenopausal Women with Advanced Breast Cancer Whose Disease Had Progressed after Tamoxifen Therapy
Parameter AROMASIN
(N = 366)
Megestrol Acetate
(N = 403)
Median Age (range) 65 (35–89) 65 (30–91)
ECOG Performance Status
  0 167 (46%) 187 (46%)
  1 162 (44%) 172 (43%)
  2 34 (9%) 42 (10%)
Receptor Status
  ER and/or PgR + 246 (67%) 274 (68%)
  ER and PgR unknown 116 (32%) 128 (32%)
    Responders to prior tamoxifen 68 (19%) 85 (21%)
    NE for response to prior tamoxifen 46 (13%) 41 (10%)
Site of Metastasis
  Visceral ± other sites 207 (57%) 239 (59%)
  Bone only 61 (17%) 73 (18%)
  Soft tissue only 54 (15%) 51 (13%)
  Bone & soft tissue 43 (12%) 38 (9%)
Measurable Disease 287 (78%) 314 (78%)
Prior Tamoxifen Therapy
  Adjuvant or Neoadjuvant 145 (40%) 152 (38%)
  Advanced Disease, Outcome
    CR, PR, or SD ≥ 6 months 179 (49%) 210 (52%)
    SD < 6 months, PD or NE 42 (12%) 41 (10%)
Prior Chemotherapy
  For advanced disease ± adjuvant 58 (16%) 67 (17%)
  Adjuvant only 104 (28%) 108 (27%)
  No chemotherapy 203 (56%) 226 (56%)

The efficacy results from the comparative study are shown in Table 10. The objective response rates observed in the two treatment arms showed that AROMASIN was not different from megestrol acetate. Response rates for AROMASIN from the two single-arm trials were 23.4% and 28.1%.

Table 10. Efficacy Results from the Comparative Study of Postmenopausal Women with Advanced Breast Cancer Whose Disease Had Progressed after Tamoxifen Therapy
Response Characteristics AROMASIN
(N=366)
Megestrol Acetate
(N=403)
Abbreviations: CR = complete response, PR = partial response, SD = stable disease (no change), TTP = time to tumor progression, C.I. = confidence interval, MA = megestrol acetate, AR = AROMASIN
Objective Response Rate = CR + PR (%) 15.0 12.4
    Difference in Response Rate (AR-MA)
2.6
    95% C.I. 7.5, -2.3
CR (%) 2.2 1.2
PR (%) 12.8 11.2
  SD ≥ 24 Weeks (%) 21.3 21.1
Median Duration of Response (weeks) 76.1 71.0
Median TTP (weeks) 20.3 16.6
    Hazard Ratio (AR-MA) 0.84

There were too few deaths occurring across treatment groups to draw conclusions on overall survival differences. The Kaplan-Meier curve for time to tumor progression in the comparative study is shown in Figure 2.

Figure 2. Time to Tumor Progression in the Comparative Study of Postmenopausal Women With Advanced Breast Cancer Whose Disease Had Progressed After Tamoxifen Therapy
Figure 2

What's New

No Current Announcements.

Therapeutic Area

Contact Pfizer Medical

Report an Adverse Event
1-800-438-1985

Search

Please enter your search term(s) for AROMASIN®

Contact Pfizer

Need to report an Adverse Event, Side Effect or Product Quality Concern?

Contact Pfizer Safety to report an adverse event, side effect or concern about the quality of a Pfizer product: (800) 438-1985

You may also contact the U.S. Food and Drug Administration (FDA) directly to report adverse events or product quality concerns at 1-800-FDA-1088 or www.fda.gov/MedWatch

Have a Medical Question on a Pfizer Prescription Medicine?
Contact Pfizer Medical Information to speak with a professional regarding your medical question on a Pfizer prescription product: (800) 438-1985
Have a Question on a Pfizer Over-the-Counter Product?
For Pfizer Consumer Healthcare non-prescription or over-the-counter products such as Advil, Centrum, Nexium or Thermacare, call (800) 322-3129
Have a Question about Pfizer Clinical Trials?
If you are looking for information about Pfizer studies currently recruiting new patients in your area, you can begin your search on our website. For questions about a Pfizer Clinical Trial, call (800) 718-1021 or email [email protected]
Need Information on Pfizer’s Patient Assistance Programs?

Pfizer RxPathways® connects eligible patients, regardless of their insurance status, to a range of assistance programs that offer insurance support, co-pay help, and medicines for free or at a savings. For more information, please call (844) 989-7284 or visit www.PfizerRxPathways.com.

Eligible patients can register for valuable savings offers for nearly 40 brand name medications. Visit www.MyPfizerBrands.com for more information.