Abstract P2-13-07: Long-term follow-up data of the side effect profile of anastrozole compared with tamoxifen in Japanese women: findings from N-SAS BC03 trial.
Authors: Iwata H , Ohsumi S , Aogi K , Hozumi Y , Imoto S , Mukai H , Yokota I , Yamaguchi T , Ohashi Y , Watanabe T , Takatsuka Y , Aihara T 
Published: August 2014

Abstract
Background: Aromatase inhibitors (AIs) are standard treatment in the adjuvant setting such as initial, switch and extended treatment in postmenopausal hormone-sensitive breast cancer patients overseas. Non-steroidal AIs have usually been used as adjuvant treatment in Japanese practice. We already reported the efficacy and short term adverse events by switching therapy from tamoxifen (TAM) to anastrozole (ANA) in Japan (Breast Cancer Res Treat. 2010;121:379–87). However, the usage of adjuvant hormone therapy currently shows a trend to continue for a long time. Furthermore, long-term follow-up data is very important for the safe use of AIs. Off course, there are many data on safety profiles in Western countries. However, there are limited data in the Asian population.
Methods: We investigated the planned analyses by using the data of a randomized adjuvant study of tamoxifen alone versus sequential tamoxifen and anastrozole in hormone-responsive postmenopausal breast cancer patients (N-SAS BC 03 trial. UMIN CTRID: C000000056). We examined the chronological changes from baseline to 36 months after randomization between the TAM arm (351 cases) and the ANA arm (345 cases) according to the case report forms (CRFs). We prospectively collected the data and compared data on hot flushes, nausea & vomiting, anorexia, fatigue, mood distress, headaches, arthralgia, leukocytopenia, liver transaminase changes, thromboembolism, vaginal bleeding, vaginal discharge, cardio-vascular events, second primary cancer and contra-lateral breast cancer between the two arms every 3 months from baseline to 12 months, and every 6 months up to 36 months after randomization. The data were expressed as the difference in the incidence over the time course and were analyzed using chi-square tests and logistic regressions with the baseline value as a covariate via generalized estimating equation using robust standard errors.
Results: The incidence of arthralgia are significantly better in the TAM arm than the ANA arm (p = 0.00002). However, there are no differences concerning all events excluding arthralgia between the two arms. Ten and twelve cases of second primary cancer occurred in the TAM and ANA arms, respectively (p = 0.6). Six and three cases of contralateral breast cancer occurred in the TAM and ANA arms, respectively (p = 0.3). According to analyses of the chronological changes, significant changes were observed in hot flushes (p = 0.001) and vaginal discharge (P &lt; 0.001) in favor of ANA, and it developed gradually after randomization and continued until 36 months after randomization. Adverse events of arthralgia increased chronologically up to 12 months after randomization in the ANA arm, but the difference between the two arms gradually decreased up to 36 months after randomization. Interestingly, concerning the liver transaminase change, the TAM arm is better until 9 months after randomization and the ANA arm is better from 12 months. There are no other differences between the two arms.
Conclusion: Safety profiles of ANA were confirmed by long-term follow-up data of a clinical trial in Japanese women. Adjuvant switch ANA therapy is also one of the standard hormone treatments for hormone-sensitive postmenopausal Japanese women.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-13-07.