Advances in our understanding of the underlying molecular mechanisms in the development of breast cancer have been at the forefront of recent clinical research. Many of the American Society of Clinical Oncology 2010’s hottest sessions featured clinical trials that looked at combination therapies with targeted agents as well as clinical improvements in standard-of-care in breast cancer.
Phase III Trial: Sunitinib/Capecitabine vs Capecitabine(Drug information on capecitabine) in Advanced Breast Cancer
Sunitinib, an oral multi-targeted tyrosine kinase inhibitor, has demonstrated single-agent activity in pretreated women with metastatic breast cancer. The clinical efficacy of this agent led investigators to conduct a phase III trial of sunitinib in combination with capecitabine vs. capecitabine alone in previously treated advanced breast cancer.
The primary endpoint of the phase III study was progression-free survival (PFS) based on the hypothesis of attaining a 50% increase in median PFS from 4 to 6 months in the intent-to-treat population. Secondary endpoints included an assessment of PFS by local investigators, overall response rate, overall survival, and safety. The patients were randomized to combination therapy with capecitabine 2,000 mg/m2 per day, orally, days 1-14 every 3 weeks plus sunitinib 37.5 mg per day or to capecitabine alone 2,500 mg/m2 per day, days 1-14 every 3weeks.
According to the authors, the study did not meet its primary endpoint; sunitinib in combination with capecitabine did not improve efficacy when compared with capecitabine alone, thus, the sunitinib plus capecitabine regimen is not recommended for second- and third-line treatment of metastatic breast cancer.
Neoadjuvant Hormone Therapy, Promising Results in Breast Cancer
Findings from the first head-to-head trial of aromatase inhibitors showed that these agents have efficacy in postmenopausal women with early ER-positive breast cancer. The 374 women with ER-positive, stage II or III breast cancer who were enrolled in the randomized, open-label, phase II trial―ACOSOG (American College of Surgeons Oncology Group) Z1031 Cohort A―had high, statistically indistinguishable overall rates of clinical response regardless of whether they received exemestane(Drug information on exemestane) (69%), letrozole (79%), or anastrozole(Drug information on anastrozole) (77%). Further, slightly more than half of those women who were candidates for mastectomy were able to undergo breast-conserving surgery after this therapy.
The women were randomly assigned to receive exemestane (25 mg/day), letrozole(Drug information on letrozole) (2.5 mg/day), or anastrozole (1 mg/day) for 16 weeks. Their tumors were measured with calipers, and clinical responses were classified using WHO criteria.
According to the results, the authors concluded that neoadjuvant aromatase inhibitor therapy should be routinely considered in appropriate postmenopausal, ER-positive, stage II/III breast cancer to improve surgical outcomes.
Early Breast Cancer: Intraoperative vs External Beam Radiotherapy
A randomized TARGIT-A (Targeted Intraoperative Radiotherapy-A) trial, conducted among more than 2,000 women, found that a single dose of radiotherapy delivered to the tumor bed during breast-conserving surgery is as safe and effective as the usual multi-week course of postoperative radiotherapy for women with early breast cancer.
In the intraoperative radiotherapy group, patients received a single dose of radiation with Intrabeam, a system that delivers radiation directly to a tumor bed during surgery. In the external-beam radiotherapy group, patients received whole-breast radiotherapy (45-50 Gy in 15-25 fractions), with or without a boost (10-16 Gy in 5-8 fractions).
Results of the trial were based on 1,113 patients in the intraoperative radiotherapy group and 1,119 patients in the external-beam radiotherapy group. They had a median age of 63 years and a median tumor size of 1.2 cm; 17% had positive lymph nodes. The estimated 4-year rate of local recurrence was 1.2% with intraoperative radiotherapy and 0.95% with external-beam radiotherapy, a nonsignificant difference.
Promising Novel Agent in Advanced Breast Cancer
According to the authors, prior to the EMBRACE study (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice vs Eribulin [E7389]), no single-agent phase III clinical trial has demonstrated improved survival in women with heavily pre-treated metastatic breast cancer.
Patients were randomized to receive either eribulin (1.4 mg/m2 administered intravenously for 2-to-5 minutes on days 1 and 8 of a 21-day treatment cycle) or treatment of physician’s choice (TPC), which was defined as any single agent chemotherapy, hormonal or biological therapy approved for cancer; or palliative radiotherapy administered according to local practice. The median age of the participants was 55 (range 27-85); 16% of patients had HER-2 positive breast cancer and 19% had triple-negative breast cancer.
The EMBRACE study met its primary endpoint of overall survival, showing that patients who received eribulin survived a median of 2.5 months longer than patients who received TPC― overall survival of 13.12 months vs 10.65 months, respectively. Results from EMBRACE also demonstrated that a secondary endpoint of overall response rate was statistically significant.
