AROMASIN
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Patients treated with AROMASIN had a higher objective response rate compared with megestrol acetate (15% vs 12%)[1]
What is the next treatment step for Kathy M.*?
*Not an actual patient. Model is used for illustrating purposes only.
- Patient characteristics:
- 63 years of age, 7 years postmenopausal
- Family history of breast cancer: mother
- 3.2-cm infiltrating ductal carcinoma in left breast
- Treatment and present status
- Lumpectomy
- Tumor was ER+, PgR+, and HER2-. Axillary dissection revealed 1 positive lymph node
- At diagnosis, metastatic work-up was negative
- Patient received radiation therapy to the left breast followed by adjuvant endocrine therapy with tamoxifen
- After 36 months of adjuvant tamoxifen, patient presented with fatigue and lower back pain
- Bone scan revealed lytic lesions in lumbar spine and ribs bilaterally
- X-ray revealed an osteolytic lesion in L4
- Tamoxifen has been the mainstay of hormonal therapy in postmenopausal women with breast cancer for more than 30 years followed by megestrol acetate and then aminogluthethimide. Based on data from large clinical trials, including the study by Kaufmann and colleagues described below, aromatase inhibitors are now used after failure of tamoxifen therapy[4]
Study design and patient characteristics in the 2 treatment arms: AROMASIN vs megestrol acetate in postmenopausal women with advanced breast cancer who experienced failure of tamoxifen
- This was a randomized double-blind, multicenter, phase 3 trial, comparing AROMASIN 25 mg daily with megestrol acetate 40 mg 4 times daily in 769 postmenopausal women with progressive breast cancer who experienced failure of tamoxifen[1]
- Women enrolled in this study were estrogen receptor (ER) and/or progesterone receptor (PgR) positive or unknown[1]
- Patient characteristics in the 2 treatment arms were comparable[1] (Table 3-1)
- Nearly 40% of patients in each treatment group experienced progressive disease while receiving adjuvant therapy with tamoxifen[1]
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| Abbreviations: CR, complete response; ECOG, Eastern Cooperative Oncology Group; ER, estrogen receptor; PD, progressive disease; PgR, progesterone receptor; PR, partial response; SD, stable disease. |
- This study was designed to demonstrate equivalence in the primary efficacy variable of objective response (OR) rate (Table 3-2). Median duration of overall success, time to tumor progression (TTP), survival, and quality of life (QoL) were also assessed. Overall success was defined as complete response (CR) plus partial response (PR) plus stable disease (SD) for at least 24 weeks. Response rates are determined based on World Health Organization criteria[1]
- Median follow-up duration was 49 weeks. Patients treated with AROMASIN had a higher OR rate compared with megestrol acetate (15% vs 12%), but the difference was not statistically significant[1] (Table 3-2). The protocol-defined hypothesis of equivalence was met
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| Abbreviations: CR, complete response; OR, objective response; PD,
progressive disease; PR, partial response; SD, stable disease; TTP,
time to tumor progression; NR, not reached. *Shown when statistically significant. †There were too few deaths to draw conclusions regarding overall survival. |
- Major time dependent variables, including median duration of overall success, median TTP (Figure 3-2), and median overall survival favored AROMASIN (see Table 3-2). However, at the time of analysis there were too few deaths to draw conclusions about overall patient survival[2]
| AROMASIN | NA | |
|---|---|---|
| Median TTP (wk) | 20.3 | 18.6 |
| Log-rank Probability | P=0.037 | |
| Relative Risk Reduction | P=0.023 | |
- When OR was assessed based on prior response to hormone therapy, patients who progressed during or following adjuvant tamoxifen and patients with metastatic disease previously responding to tamoxifen responded better to AROMASIN[1,2] (Table 3-3)
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- AROMASIN demonstrated antitumor activity in metastatic and adjuvant tamoxifen failures vs megestrol acetate[1]
- Median time of progression was 20.3 weeks for AROMASIN vs 16.6 weeks for megestrol acetate (P = .037)
- Median duration of response was 76.1 weeks for AROMASIN vs 71 weeks for megestrol acetate
- Overall success rate for AROMASIN was 37.4% vs 34.6% for megestrol acetate
Adverse events
- In this study of advanced breast cancer, only 3% of patients on AROMASIN discontinued treatment due to adverse events. Most common adverse events were mild to moderate and included: hot flushes (13% vs 5%), nausea (9% vs 5%), fatigue (8% vs 10%) increased sweating (4% vs 8%), and increased appetite (3% vs 6%) for AROMASIN vs megestrol acetate, respectively[1]
AROMASIN® (exemestane tablets)
AROMASIN is indicated for adjuvant treatment of postmenopausal women with estrogen receptor-positive early breast cancer who have received 2 to 3 years of tamoxifen and are switched to AROMASIN for completion of a total of 5 consecutive years of adjuvant hormonal therapy.
AROMASIN is indicated for the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.
Important Safety Information
AROMASIN (exemestane tablets) should not be used in women who are premenopausal, are nursing or pregnant, have a known hypersensitivity to the drug, or are taking estrogen-containing agents.
Dose modification is recommended for patients who are receiving certain medications, including strong CYP 3A4 inducers such as rifampicin and phenytoin.
In patients with early breast cancer, elevations in bilirubin, alkaline phosphatase, and creatinine were more common in those receiving exemestane than either tamoxifen or placebo.
Reductions in bone mineral density over time are seen with AROMASIN use.
Incidence of adverse events (AEs; %) occurring in ≥10% of patients in any treatment group (AROMASIN vs tamoxifen) in the Intergroup Exemestane Study (IES): hot flushes (21.2 vs 19.9), fatigue (16.1 vs 14.7), arthralgia (14.6 vs 8.6), headache (13.1 vs 10.8), insomnia (12.4 vs 8.9), and increased sweating (11.8 vs 10.4).
In IES, discontinuation rate due to AEs was similar between AROMASIN and tamoxifen (6.3% vs 5.1%). Incidence of cardiac ischemic events (myocardial infarction, angina, and myocardial ischemia): AROMASIN 1.6%, tamoxifen 0.6%. Incidence of cardiac failure: AROMASIN 0.4%, tamoxifen 0.3%.
Most common adverse events reported for advanced breast cancer were mild to moderate and included hot flashes (13%), nausea (9%), fatigue (8%), increased sweating (4%), and increased appetite (3%).
References
- Kaufmann M, Bajetta E, Dirix LY, et al, for the Exemestane Study Group. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial. J Clin Oncol. 2000;18:1399-1411.
- AROMASIN [package insert]. New York, NY: Pfizer Inc; 2005.
- Data on file, Pfizer Inc. New York, NY.
- Campos S. Aromatase inhibitors for breast cancer in postmenopausal women. The Oncologist. 2004;9:126-136.
