New Treatment Options in Advanced Breast Cancer

Laurie Barclay, MD

December 11, 2002

Dec. 11, 2002 — Two presentations at the 25th Annual San Antonio Breast Cancer Symposium on Dec. 11 suggest new treatment options in advanced breast cancer refractory to conventional chemotherapy. A double-blind crossover trial showed that anastrozole (ARI) should be given as first-line adjuvant therapy with tamoxifen (TAM) used after first progression for women with advanced breast cancer. Another trial found that fulvestrant is efficacious even after failure of both tamoxifen and aromatase inhibitors.

"In patients with endocrine-responsive disease and indication for second-line endocrine therapy, ARI showed longer time-to-progression than TAM when given as first-line therapy," write B. Thuerlimann and colleagues from Berne, Switzerland. "After crossover, both ARI and TAM have similar activity. These results are supportive of the recommendation to give ARI as first-line treatment for advanced breast cancer in postmenopausal women with estrogen and/or progesterone receptor-positive disease."

In the SAKK Trial 21/95, a substudy of Anastrozole Trial 0027, 60 patients randomized in Swiss centers were followed through both the first-line therapy and the subsequent crossover phase. Median age was 68 years (range, 47 - 85 years). The most common sites of metastatic disease were bone in 45 patients, lung in 28, skin in 24, and nodes in 17. Estrogen and/or progesterone receptors (ER/PgR) were positive in 56 and unknown in four patients.

Median time to progression (TTP) on first-line therapy for 60 randomized patients was 11.3 months for ARI and 8.3 months for TAM (P = .75 by log-rank test). After progression, 19 patients switched from ARI to TAM, and 18 patients switched from TAM to ARI. Median TTP on first-line therapy for the 37 patients who subsequently crossed over was 16.3 months for ARI and 5.9 months for TAM. Median TTP was six months for both second-line treatments. Median time from randomization to second progression was 28.2 months for the sequence ARI-TAM and 19.5 months for the sequence TAM-ARI (P = .36).

"Both treatment sequences have shown clinically relevant efficacy," the authors write.

The second presentation, by L. Perey and colleagues from Switzerland, described results with fulvestrant (formerly ICI 182,780) as hormonal treatment in postmenopausal patients with advanced breast cancer who had progressed after treatment with tamoxifen and aromatase inhibitors.

Fulvestrant "is a new class of antiestrogen that is completely free of agonist activity," the authors write. "In postmenopausal women with advanced breast cancer progressing on prior endocrine therapy, it has shown activity similar to the aromatase inhibitor anastrozole."

This ongoing phase II, open, multicenter, noncomparative trial has to date followed 20 postmenopausal women with advanced breast cancer for at least six months. These subjects had received prior endocrine treatment with tamoxifen and nonsteroidal aromatase inhibitors, but the inclusion criteria were subsequently modified to include patients progressing after treatment with steroidal aromatase inhibitors.

Median age was 67 years (range, 45 - 86 years). Metastases involved bone in 14 patients, liver in nine, skin in four, lymph nodes in three, breast in three, and lung in two. Of 12 patients who had received prior chemotherapy, five had one line of chemotherapy for metastatic disease. All patients received anastrozole or letrozole as second-line treatment for advanced breast cancer except for two patients, who received an aromatase inhibitor as first-line treatment after progression on adjuvant tamoxifen.

Of the 20 patients followed thus far, 10 had progression and three were ineligible. However, two had a partial response and five had stable disease for at least 24 weeks, which represents 41% of eligible patients.

Adverse effects were grade 1 and 2, and included fatigue in three patients, chills in three, nausea and vomiting in three, constipation in two, hot flashes in two, and stomatitis in two patients.

"In this heavily pre-treated population, a clinical benefit with fulvestrant (partial response or stable disease at 24 weeks) was observed in 41% of eligible patients after tamoxifen and aromatase inhibitor failure," the authors write. "Fulvestrant is a potential alternative treatment option for postmenopausal women with advanced breast cancer, progressing on aromatase inhibitors."

25th Annual SABCS: Abstracts 255, 249. Presented Dec. 11, 2002.

Reviewed by Gary D. Vogin, MD

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