AROMASIN
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Adverse events are usually mild to moderate in postmenopausal women treated with AROMASIN®.
AROMASIN tolerability in advanced breast cancer clinical trials
- AROMASIN 25 mg daily was evaluated in 1058 patients treated in the clinical trials. AROMASIN is generally well tolerated and adverse events were usually mild to moderate[1]
- The incidence (%) of adverse events of all Common Toxicity Criteria (CTC) grades, regardless of causality, reported in ≥5% of patients with advanced breast cancer enrolled in a randomized, double-blind, multicenter, multinational study comparing AROMASIN (N = 358) with megestrol acetate (N = 400)[1] is summarized in Table 4-2
| Body system and adverse event by MedDRA dictionary | %
of Patients |
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Table 4-1. Safety Profile of AROMASIN vs Tamoxifen in
IES at 34.5-month median follow-up. The incidence (%) of adverse events
of all CTC grades and the incidence of illness occurrence in ≥5% of
patients in treatment group in the IES[1]
*75 patients received tamoxifen 30 mg daily. †Events actively sought.
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Table 4-2. Adverse events (%) of all grades and cases
reported in at least 5% of patients in each treatment arm of the phase 3
pivotal trial in metastatic breast cancer[1]
*Includes edema, peripheral edema, leg edema.
IES safety data from 32 month follow-up
- AROMASIN was generally well tolerated and adverse events were usually mild to moderate[1] (Table 4-1)
- Discontinuation due to adverse events occurred in 6.3% and 5.1% of patients receiving AROMASIN and tamoxifen, respectively[1]
- Deaths due to any cause were reported for 1.3% of patients treated with AROMASIN and 1.4% of the tamoxifen-treated patients[1]
| Body system and adverse event by MedDRA dictionary | %
of Patients |
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Table 4-3. Safety Profile of AROMASIN vs Tamoxifen in
IES at 34.5-month median follow-up. The incidence (%) of adverse events
of all CTC grades and the incidence of illness occurrence in ≥5% of
patients in treatment group in the IES[1]
*75 patients received tamoxifen 30 mg daily. †Events actively sought.
Most common adverse events (AEs) after long-term follow-up
- The most common AEs observed at the 52.4-month median follow-up were similar to those observed at the 34.5-month median follow-up[1,2]
- At the 52.4-month median follow-up, patients taking AROMASIN experienced a significant increase in the overall fracture rate vs tamoxifen: 7% vs 4.9%
(P = 0.002)[2] - Reductions in bone mineral density over time are seen with use of AROMASIN[1]
AROMASIN effects on bone in early breast cancer
- Estrogen has a role in maintaining bone mineral density (BMD)[3] Therefore, strategies that reduce estrogen levels have a potential to reduce BMD
- 2 studies address the effect of AROMASIN on BMD[4,5]
- AROMASIN vs placebo-controlled study[4] (Table 4-4) (027)
- Objective:
- Examine and evaluate the effects of AROMASIN on bone in a randomized, placebo-controlled study in low-risk postmenopausal women with early breast cancer[1,6]
- Study design:
- 147 women with early breast cancer at low risk of relapse and not given adjuvant therapy were randomized to treatment with AROMASIN 25 mg daily or placebo for 24 months[6]
- Key exclusion criteria included prior history or current condition of chronic bone disease; use of calcium supplements exceeding 500 mg daily; vitamin D use within 6 month of enrollment; and previous treatment with bisphosphonates[6]
- The median age of women enrolled in the study was approximately 60 years, and all were a median of 8 (placebo) to 10 (AROMASIN) years past menopause[6]
- Results:
- No patients (in either group) with normal BMD at baseline developed osteoporosis[6]
- Fractures were reported in 4 patients treated with AROMASIN and in 5 patients receiving placebo[6]
- One year after withdrawal of AROMASIN, partial reversal of BMD changes in the lumbar spine and femoral neck was observed[4]
- IES trial: AROMASIN vs tamoxifen bone substudy[5] (Table 4-3)
- Study design:
- See IES study
- Data for bone substudy are available for 206 women[5]
- Concomitant use of bisphosphonates, vitamin D supplements, and calcium was not allowed during or 6 months prior to study[1]
- Results:
- Clinical fractures were reported in 94 patients receiving AROMASIN (4.2%) and 71 patients receiving tamoxifen (3.1%)[1]
- Osteoporosis was reported in 4.6% of patients treated with AROMASIN and 2.8% of patients treated with tamoxifen[1]
- Reductions in BMD over time are seen with AROMASIN[1]
- In the main IES trial, switching to AROMASIN was associated with a higher incidence of clinical fracture and osteoporosis compared with continuation on tamoxifen therapy[1]
| BMD |
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| Lumbar spine |
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| Femoral neck |
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Table 4-4. Percent Change in BMD from Baseline to 24
Months in Patients Receiving AROMASIN Compared with Patients Receiving Tamoxifen
(IES) or Placebo (Study 027)[1] *For patients
who had 24-month data.
Contraindications, warnings, precautions
- AROMASIN is contraindicated in patients with a known hypersensitivity to the drug or to any of the excipients[1]
- AROMASIN Tablets may cause fetal harm when administered to a pregnant woman. There are no studies in pregnant women using AROMASIN. AROMASIN is indicated for postmenopausal women. If there is exposure to AROMASIN during pregnancy, the patient should be apprised of the potential hazard to the fetus and potential risk for loss of the pregnancy[1]
- AROMASIN Tablets should not be administered to premenopausal women. AROMASIN should not be coadministered with estrogen-containing agents as these could interfere with its pharmacologic action[1]
- In patients with early breast cancer, elevations in bilirubin, alkaline phosphatase, and creatinine were more common in those receiving AROMASIN than either tamoxifen or placebo[1]
- It is not known whether AROMASIN is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if a nursing woman is inadvertently exposed to AROMASIN[1] (see WARNINGS in prescribing information)
- The safety and effectiveness of AROMASIN in pediatric patients have not been evaluated[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
- AROMASIN [package insert]. New York, NY: Pfizer Inc; 2005.
- Data on file. Pfizer Inc. New York, NY.
- Riggs BL, Khosla S, Melton LJ III. A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res. 1998;13:763-773.
- Lønning PE, Geisler J, Krag LE, et al. Changes in bone metabolism after 2 years’ treatment with exemestane (E) in postmenopausal women with early breast cancer (EBC) at low risk: follow-up (FU) results of a randomized placebo-controlled study. J Clin Oncol. 2005;23(16S). Abstract 531.
- Coleman RE, Banks LM, Girgis SI, et al, on behalf of the Intergroup Exemestane Study (IES). Exemestane Study (IES): Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study. Lancet Oncol. 2007; 8:119-127.
- Lønning PE, Geisler J, Krag LE, et al. Effects of exemestane administered for 2 years versus placebo on bone mineral density, bone biomarkers, and plasma lipids in patients with surgically resected early breast cancer. J Clin Oncol. 2005;23:5126-5137.
