Practice Update: Oncology

BREAST 28

Adjuvant Tamoxifen and Exemestane inWomen With Postmenopausal Early Breast Cancer The Lancet Oncology Take-home message • This extended follow-up of a phase III trial was designed to assess outcomes with different hormone therapy combinations in postmenopausal patients with early-stage, hormone receptor–positive breast cancer. Patients were randomized to either 5 years of exemestane monotherapy or to a sequential scheme of tamoxifen for 2.5 to 3.0 years followed by exemestane, for a total duration of 5 years. After a median follow-up of 9.8 years, disease-free survival was similar between the groups. • These results suggest that both approaches are reasonable for adjuvant endocrine therapy in postmenopausal women.

Abstract BACKGROUND After 5 years of median follow-up, the Tamoxifen Exemestane Adjuvant Multina- tional (TEAM) trial reported no difference in disease-free survival between exemestane monotherapy and a sequential scheme of tamoxifen followed by exemestane in post- menopausal patients with early-stage, hormone receptor-positive breast cancer. As recurrence risk in hormone receptor-positive breast cancer remains linear beyond 5 years after diagnosis, COMMENT By Annette Hasenburg Prof. Dr. med L ong-term findings of the TEAM study – a randomized, open-label phase III trial comparing 5 years of exemestane with 2 to 3 years of tamox- ifen followed by exemestane as adjuvant therapy for postmenopausal patients with hormone receptor (HR)-positive breast cancer – are presented in the July 2017 issue of The Lancet Oncology . After a median follow-up of 9.8 years of 6120 patients in 9 countries, 10-year disease-free survival was 67% in both arms. Even patients with low-risk tumors continued to relapse over time despite endocrine therapy. Breast cancer recurrence was lower in the exemestane group (20%; 95% CI, 19–22) than in the sequential arm (22%; sub-dis- tribution HR for recurrence-free interval 0.88, 95% CI 0.79–0.99), but other-cause mortality was higher with exemestane. There seems to be a trade-off between toxic effects and efficacy, resulting in sim- ilar overall survival in both arms.

we analysed long-term follow-up outcomes of this trial. METHODS The TEAM trial, a multicentre, open-la- bel, randomised, controlled, phase 3 trial, included postmenopausal patients with ear- ly-stage hormone receptor-positive breast cancer from nine countries. Patients were randomly allocated (1:1) by a computer-gener- ated random permuted block method (block sizes 4-8) to either 5 years of oral exemestane

monotherapy (25 mg once a day) or a sequen- tial scheme of oral tamoxifen (20 mg once a day) followed by exemestane for a total dura- tion of 5 years. After the publication of the IES trial, the protocol was amended (Dec 13, 2004). Patients assigned to tamoxifen were switched after 2•5-3•0 years to exemestane therapy for a total duration of 5•0 years of treatment. Ran- domisation was done centrally in each country. Long-term follow-up data for disease recurrence and survival was collected in six participating countries and analysed by intention to treat. The primary endpoint was disease-free survival at 10 years of follow-up. FINDINGS 6120 patients of the original 9776 patients in the TEAM trial were included in the current intention-to-treat analysis. Median follow-up was 9•8 years (IQR 8•0-10•3). Dur- ing follow-up, 921 (30%) of 3075 patients in the exemestane group and 929 (31%) of 3045 patients in the sequential group had a dis- ease-free survival event. Disease-free survival at 10 years was 67% (95% CI 65-69) for the exemes- tane group and 67% (65-69) for the sequential group (hazard ratio 0•96, 0•88-1•05; p=0•39). INTERPRETATION The long-term findings of the TEAM trial confirm that both exemestane alone and sequential treatment with tamoxifen fol- lowed by exemestane are reasonable options as adjuvant endocrine therapy in postmeno- pausal patients with hormone receptor-positive early breast cancer. These results suggest that the opportunity to individualise adjuvant endo- crine strategy accordingly, based on patient preferences, comorbidities, and tolerability might be possible. Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2017 Jul 18;[EPub Ahead of Print], MGM Derks, EJ Blok, C Seynaeve, et al. www.practiceupdate.com/c/55992

There was no identification of any clin- icopathological subgroup that showed a benefit from either strategy. Hope for the future is to find biomarkers that will allow a better stratification of patients. Both strategies are reasonable options for postmenopausal women with HR-positive breast cancer, and should be selected according to the patient’s risk profile and the possible side effects. Two questions will still have to be answered: 1) optimum length of treatment and 2) combination of antihormonal drugs with other components to overcome endocrine resistance (eg, CDK 4–6 inhib- itors).

Dr Hasenburg is Director of Obstetrics and Gynecology Mainz University Medical Center, Mainz, Germany.

PRACTICEUPDATE ONCOLOGY