(ChemotherapyAdvisor) – Long-term updates from the Austrian Breast and Colorectal Cancer Study Group 8 (ABCSG-8), which enrolled women to either tamoxifen for 5 years or to 2 years of tamoxifen followed by 3 years of the aromatase inhibitor (AI) anastrozole, led to small benefits in outcome and less toxicity, according to results published ahead of print in the Journal of Clinical Oncology.

The prospective, multicenter, open-label ABCSG-8 trial is, with part of the four-arm option in the BIG 1-98 study, the only large phase 3 trial exploring sequential therapy of an AI with tamoxifen monotherapy, according to Peter C. Dubsky, MD, of the Medical University of Vienna, Vienna, Austria, and colleagues. The trial randomly assigned 3,714 postmenopausal women ages 80 years or younger with primary, operable, histologically verified estrogen or progesterone receptor positive grade 1 or 2 ductal and G1 or G2 lobular invasive breast cancer to either the sequence or the monotherapy arm immediately following surgery. No neoadjuvant chemotherapy was allowed.

At a median of 60 months of follow-up, median age was 63.8 years, 75% were node negative, and 75% had T1 tumors among the 17,563 woman-years included. Women assigned to the tamoxifen-anastrozole sequence showed a nonsignificant 20% reduction in recurrence risk, the study’s primary end point. “The small efficacy benefits observed were driven by a lower number of distant metastases and deaths,” the investigators wrote. Disease-free survival at 5 years was 89.5% in the sequence arm and 88.5% in the monotherapy arm, adding “to the clinical evidence indicating that these subgroups can be spared cytotoxic treatment.” Adverse events were those associated with the toxicity profiles of the agents; however, continued treatment with tamoxifen led to a one-third increase in endometrial hyperplasia and polyps.

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An accompanying editorial notes that current American Society of Clinical Oncology guidelines recommend postmenopausal women “consider incorporating AI therapy at some point during adjuvant treatment, either as up-front therapy or as sequential treatment after tamoxifen.” However, total AI exposure is limited to 5 years and “optimal timing and duration of endocrine treatment remain unresolved,” despite the ABCSG-8 trial results.

“In our treatment setting, we recommend a switch to an aromatase inhibitor after 2 years if a patient is on tamoxifen,” Dr. Dubsky told ChemotherapyAdvisor.com.

Jakesz, American Society of Clinical Oncology, 2011
Burstein, American Society of Clinical Oncology, 2012