Exemestane an effective, well-tolerated first-line treatment for postmenopausal women with metastatic breast cancer

Exemestane, a steroidal aromatase inactivator, elicits better early response, compared to tamoxifen, as first-line therapy in postmenopausal women with metastatic breast cancer, according to recently published data. The drug appears safe and is well tolerated, but it provides no overall long-term or survival benefit, compared to tamoxifen. The European Organisation for the Research and Treatment of Cancer (EORTC) Breast Cancer Cooperative Group conducted this open-label, randomized trial...

Exemestane, a steroidal aromatase inactivator, elicits better early response, compared to tamoxifen, as first-line therapy in postmenopausal women with metastatic breast cancer, according to recently published data. The drug appears safe and is well tolerated, but it provides no overall long-term or survival benefit, compared to tamoxifen.

The European Organisation for the Research and Treatment of Cancer (EORTC) Breast Cancer Cooperative Group conducted this open-label, randomized trial in 81 centers. The published data incorporates results from a phase II trial, which was extended into the Phase III trial published in the Journal of Clinical Oncology. In the final analysis, 2 centers (11 patients) were excluded from the results due to inadequate record keeping.

A total of 382 postmenopausal patients with metastatic breast cancer (MBC) were randomized to receive either exemestane (n=190; 25 mg orally, once daily) or tamoxifen (n=192; 20 mg orally, once daily). Patients continued their treatment until disease progression or signs of unacceptable toxicities. The groups were stratified based on study location, prior chemotherapy for metastatic disease, prior treatment with tamoxifen, and location of primary metastasis. Patients were enrolled between October 1996 and December 2002. Prior tamoxifen treatment was allowed, but the recurrence-free interval following that treatment had to be >6 months.

Patient evaluation was done at baseline, and at weeks 8, 16, and 24. Patients were then evaluated every 12 weeks until week 96, and thereafter every 24 weeks. Evaluations included physical examination, laboratory tests, and imaging studies. The primary endpoint was time to disease progression. Data analysis was done on the intent-to-treat population, which comprised 182 patients in the exemestane group and 189 patients in the tamoxifen group.

Progression free survival (PFS) at 6 months was 66.2% in the exemestane group and 49.5% in the tamoxifen group. The PFS rate at 12 months was 41.7% in the exemestane group and 31.2% in the tamoxifen group. The authors point out that although a log-rank test did not show the difference to be statistically significant, a Wilcoxon test, which is more sensitive to earlier events, revealed the median PFS (9.9 months for exemestane, 5.8 months for tamoxifen) to be statistically significant (P=.028). The tumor response rate (complete + partial) was 46% for exemestane and 31% for tamoxifen (P=.005).

Only 3 patients (1 in the exemestane group and 2 in the tamoxifen group) stopped treatment due to toxicity. The exemestane group experienced more grade 1/2 arthralgia/myalgia, and more cardiac adverse events, though a direct relationship to the treatment could not be established.

The authors conclude that exemestane is a safe and effective first-line treatment for metastatic breast cancer in postmenopausal women. It offers a significant early response that is better than tamoxifen, but is not associated with long-term survival benefits. In their opinion, "lengthening of PFS is worthwhile provided that it supports the preservation or improvement of quality of life. Quality of life is therefore an important endpoint to include in future comparable studies of AIs [aromatase inhibitors] as first-line treatment of hormone-sensitive MBC." (Paridaens RJ, et al. J Clin Oncol 2008;26:4883-4890).