Abstract P3-12-08: Evaluation of treatment compliance during extended endocrine therapy; secondary analysis of the IDEAL trial
Authors: Blok EJ , Kroep JR , Meershoek-Klein Kranenbarg E , Duijm-de Carpentier M , Nortier JWR , Rutgers EJTh , van de Velde CJH 
Published: February 2018

In the first clinical trial reports about extended endocrine therapy in early breast cancer, treatment compliance appeared as a major concern. Earlier, it was shown in the IDEAL trial that approximately 35% of all patients stopped therapy before the allocated time. This additional study was conducted to evaluate the factors contributing to early treatment discontinuation.

Methods: In the IDEAL trial, a total of 1824 patients were randomized between either 2.5 or 5 years of extended letrozole, after 5 years of any adjuvant endocrine therapy. Only eligible patients who started therapy were included in the analysis. Adverse events were collected until 30 days after last treatment dose Reasons for ending therapy were collected prospectively at the time of treatment discontinuation.

Results: The majority of early treatment discontinuation was caused by adverse events (AEs) (n=372, 20.4% of all patients, 58% of all early treatment discontinuations). The most frequently reported AEs associated to treatment discontinuation were arthralgia (n=71, 9.9% of AEs associated treatment discontinuation), fatigue (n=48, 6.7%), depression (n=47, 6.5%), hot flashes (n=47, 6.5%) and alopecia (n=39, 5.4%). Of all AEs associated to early discontinuation, 86% was grade 1 or 2 (table 1). All grade 5 events were not associated to therapy.

Table 1 - Overview of adverse events most frequently associated to early treatment discontinuation Grade 1Grade 2Grade 3Grade 4Grade 5TotalArthralgia2236121071Fatigue192610148Depression202160047Hot flashes162092047Alopecia28731039Total (all AEs)30231680136720

Furthermore, the influence of previous type of adjuvant endocrine therapy was evaluated. Of all patients initiallytreated with 5 years of tamoxifen, 29% stopped due to an AE. In contrast, patients who were treated with aromatase inhibitors during the first 5 years, either with monotherapy or after 2-3 years of tamoxifen, stopped due to AEs in 22% and 18% respectively (Pearson Chi-square p-value 0.001). The average number of AEs per patient per previous treatment group was 2.27 for tamoxifen monotherapy, 2.03 for AI monotherapy and 1.73 in the sequential group. Corrected for the number of AEs in each group, patients pre-treated with 5 years of tamoxifen had a chance of treatment discontinuation of 12.7% per AE, compared to 10.8% and 10.4% for AI monotherapy and sequential therapy respectively. Additionally, of patients that completed regular adjuvant therapy between 1 and 2 years before randomization, 34% stopped due to adverse events. In contrast, of patients that completed therapy within 6 months before randomization stopped in 19% of all cases (Pearson Chi-square p-value &lt;0.001).

Conclusion: We have shown that adverse events are an important factor in early treatment discontinuation. Furthermore, the relation between adverse events and early discontinuation is influenced by the type of earlier therapy, with the highest rate of discontinuation for AI-naïve patients. This suggests that after 5 years of tamoxifen, patients are more inclined to stop therapy when encountering new AI-related adverse events compared to patients who were pre-treated with an AI.

Citation Format: Blok EJ, Kroep JR, Meershoek-Klein Kranenbarg E, Duijm-de Carpentier M, Nortier JWR, Rutgers EJTh, van de Velde CJH. Evaluation of treatment compliance during extended endocrine therapy; secondary analysis of the IDEAL trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-12-08.