Episode 8: The DATA trial and the GIM trial: how to decide on extended endocrine therapy in Postmenopausal Breast Cancer Patients

The DATA trial systematically explored the efficacy of extended adjuvant endocrine therapy utilizing anastrozole in patients with hormonal receptor-positive, predominantly HER2-negative breast cancer. Following a 2-3 year course of tamoxifen, patients were randomly allocated into two groups: one receiving an additional 3 years and the other 6 years of anastrozole treatment.

The subsequent analysis revealed a numerical difference but lacked statistical significance in Disease-Free Survival (DFS) and Overall Survival (OS) between the varied treatment durations. Despite certain subgroup analyses indicating distinctions in OS, the overall outcome was unfavourable. One plausible explanation is that the patients included in the study cohort possessed an inherently low risk of recurrence, rendering them unresponsive to extended endocrine therapy.

In contrast, the GIM trial yielded positive results concerning DFS and OS with extended endocrine therapy involving letrozole. Notably, this study encompassed a larger proportion of high-risk patients compared to the DATA trial.

Applying these findings to contemporary clinical practice in patient consultations involves a nuanced approach. Experts advocate for tailoring the duration of extended endocrine therapy based on risk stratification. Patients at very low risk may discontinue therapy after 5 years, while the majority of intermediate-risk patients could benefit from extending therapy for 7-8 years. Conversely, patients at exceptionally high risk, such as those with >4 positive lymph nodes, large tumours, or T3 stage, may derive advantages from extended endocrine therapy for up to 10 years.

It is crucial to recognize that the landscape of breast cancer treatment has evolved, with the introduction of abemaciclib for specific high-risk patients displaying certain clinical features. Nevertheless, delineating the intermediate-risk profile for the majority of patients remains a challenging endeavour, complicating therapeutic decisions.

Several tools are available to estimate the risk of recurrence, including the widely used DCIS tool for assessing relapse risk beyond 5 years. Additionally, tools like MammaPrint and the Breast Cancer Index (BCI) test are employed in breast cancer management. However, MammaPrint does not assess the benefits of endocrine therapy. On the other hand, the BCI test, a genomic assay, is specifically designed to evaluate the potential benefits of extended endocrine treatment. Despite its potential utility, its lack of reimbursement approval in Belgium means that patients must decide to bear the cost. In practice, discussions with patients must encompass both the risk of recurrence and the potential impact of treatment-related side effects on their Quality of Life (QoL).

References:

Tjan -Heijnen V. et al. (2023). Extended adjuvant aromatase inhibition after sequential endocrine therapy in postmenopausal women with breast cancer: follow-up analysis of the randomised phase 3 DATA trial. EClinicalMedicine. 58:101901

Del Mastro L. et al. (2021). Extended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: a multicentre, open-label, randomised, phase 3 trial.. Lancet Oncol. 22(10): 1458-1461