Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands; Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
Eur J Cancer. 2018 May;95:59-67. doi: 10.1016/j.ejca.2018.03.014. Epub 2018 Apr 7.
Extended endocrine therapy beyond 5 years for postmenopausal breast cancer has been studied within multiple phase III trials. Treatment compliance in these trials is generally poor. In this analysis, we aimed to determine factors that were associated with participation in the phase III Investigation on the Duration of Extended Adjuvant Letrozole (IDEAL) trial and with early treatment discontinuation, and how this influenced survival outcome.
In the IDEAL trial, postmenopausal patients were randomised between 2.5 or 5 years of extended letrozole, after completing 5 years of endocrine therapy for hormone receptor-positive early breast cancer. A subgroup of this population participated earlier in the Tamoxifen Exemestane Adjuvant Multinational trial (5 years of exemestane or 2.5 years of tamoxifen followed by exemestane as primary adjuvant therapy) in which we explored which factors were determinative for enrolment in the IDEAL study. In the IDEAL cohort, we evaluated which factors predicted for early treatment discontinuation and the effect of early treatment discontinuation on disease-free survival (DFS).
Nodal status, younger age and adjuvant chemotherapy were significantly associated with higher enrolment in the IDEAL trial. In the IDEAL cohort, adverse events (AEs), the type of primary endocrine therapy and the interval between primary and extended therapy were associated with early treatment discontinuation. Among the reported AEs, depressive feelings (56%) were most frequently associated with early treatment discontinuation. Early treatment discontinuation was not associated with worse DFS (hazard ratio [HR] = 1.02, 95% confidence interval = 0.76-1.37).
In this analysis, we found that risk factors were most strongly associated enrolment in the IDEAL trial. In contrast, patient experiences were the most significant factors leading to early treatment discontinuation, with no effect on DFS.
多项三期临床试验研究了绝经后乳腺癌患者延长内分泌治疗超过 5 年的效果。这些试验中的治疗依从性通常较差。在这项分析中，我们旨在确定与参加三期延长辅助来曲唑治疗（IDEAL）试验以及与早期治疗中断相关的因素，并探讨其对生存结果的影响。
在 IDEAL 试验中，完成 5 年激素受体阳性早期乳腺癌内分泌治疗后，绝经后患者被随机分配接受 2.5 年或 5 年的延长来曲唑治疗。该人群的一部分更早地参加了他莫昔芬依西美坦辅助多国试验（5 年依西美坦或 2.5 年他莫昔芬，然后依西美坦作为主要辅助治疗），我们在该试验中探索了哪些因素决定了参加 IDEAL 研究。在 IDEAL 队列中，我们评估了哪些因素预测早期治疗中断，以及早期治疗中断对无病生存（DFS）的影响。
淋巴结状态、年龄较小和辅助化疗与更高的 IDEAL 试验入组率显著相关。在 IDEAL 队列中，不良事件（AE）、原发性内分泌治疗类型和原发性与延长治疗之间的间隔与早期治疗中断相关。在报告的 AE 中，抑郁感（56%）与早期治疗中断最相关。早期治疗中断与DFS 无显著相关性（危险比[HR] = 1.02，95%置信区间=0.76-1.37）。
在这项分析中，我们发现风险因素与 IDEAL 试验的入组相关性最强。相反，患者体验是导致早期治疗中断的最重要因素，但对 DFS 无影响。
