Tamoxifen/AI Sequencing as Effective as Continuous 5-Year AI Therapy

San Antonio, TX — One of the burning questions regarding endocrine therapy for hormone receptor-positive (HR) breast cancer is which strategy is better: A sequential strategy of tamoxifen upfront followed by an aromatase inhibitor (AI) for a total of 5 years or giving an AI for 5 years. Final results from the TEAM trial failed to resolve this issue; both strategies were in a dead-heat for disease-free survival (DFS), time to recurrence (TTR), and overall survival (OS).

“TEAM was the first trial prospectively powered to detect superiority of 5 years of an aromatase inhibitor [in this case, exemestane] versus sequential therapy with tamoxifen followed by AI. This large study showed that either strategy is an appropriate therapeutic option. Translational research may be able to identify subsets of patients who can benefit from each of these strategies,” said Daniel Rea, MD, University of Birmingham, U.K.

The large, open-label TEAM trial randomized 9779 women with invasive, post-menopausal, HR breast cancer to a total of 5 years of treatment applying either strategy. All women (mean age, 65 y) underwent surgical resection and none had metastases at baseline. Radiotherapy (68%) and chemotherapy (36%) were permitted. About half of the breast cancers were node-positive and all were HR .

At a median follow-up of 5.1 years, 60% of participants completed 5 years of treatment. At that time, 127 local recurrences had occurred and 820 distant metastases had been reported. More than 85% of patients in both groups were disease-free at 5 years, with no difference in outcomes observed between the two strategies (hazard ratio [HR], 0.97). Similarly, more than 90% of patients were alive with or without disease at 5 years, with no difference in OS between the two strategies (HR, 1.00). “We hardly ever see an HR of 1,” Dr Rea said.

Analysis of secondary endpoints failed to detect superiority for continuous AI therapy versus sequential tamoxifen followed by AI. No difference between strategies was seen for either TTR or nodal status at baseline.

Toxicities were as expected with both tamoxifen and exemestane. “Tamoxifen-treated patients had more tamoxifen-like adverse events, including gynecologic effects, while exemestane was associated with typical AI-like effects, such as musculoskeletal complaints,” Dr Rea said.

Vaginal toxicity was significantly greater for those initially treated with tamoxifen: There were 17 endometrial cancers in the tamoxifen-treated patients versus 7 in the group on continuous exemestane; endometrial abnormalities were reported in 187 patients versus 20 patients, respectively. Vaginal discharge and bleeding were also significantly greater in patients who took tamoxifen (P <.001 for all comparisons). Cardiovascular disorders were similar between groups, with the exception of more venous thromboses in the tamoxifen users (P <.001). “Surprisingly, we saw more hyperlipidemia in the exemestane group,” Dr Rea said.

Musculoskeletal events were significantly higher with continuous exemestane. Fractures occurred in 5% of the exemestane group versus 3.5% of those initially randomized to tamoxifen (P <.001). The incidence of osteoporosis was double: 9.9% versus 5.4% for those originally randomized to tamoxifen (P <.001). Arthralgia was reported more frequently in the exemestane-treated group (P <.001).

Women entered in the TEAM trial have no restrictions as to whether they can go on to have further endocrine therapy once the study is completed, Dr Rea said. SABCS Abstract 11.