283P - Immune-mediated secondary adrenal insufficiency is more commonly found in younger patients undergoing neoadjuvant treatment for early breast cancer

Background

Neoadjuvant therapy in early triple-negative breast cancer (eTNBC) with pembrolizumab and chemotherapy has become the new standard following the publication of KEYNOTE-522 study. While immune-related effects are expected with this treatment combination, it remains unclear if there are specific subgroups associated with increased risk of endocrine adverse events (AEs). We aimed to assess the risk of endocrine AEs in key patient subgroups undergoing neoadjuvant treatment for eTNBC.

Methods

We included consecutive pts between March 2022 and November 2023 in 11 centers across Argentina who underwent neoadjuvant chemotherapy and immunotherapy for eTNBC. Univariate and multivariate analyses including logistic regression were conducted to determine whether the rate of endocrine therapy AEs was associated with key specific subgroups, including age, pathological response, germinal BRCA status, tumor size, axillary clinical staging, and dose-dense anthracycline regimens. p < 0.05 was considered for statistical significance.

Results

A total of 143 pts were included from 13 centers. The median age was 47,2 years [IQR 23-79]. The incidence of all grade, G3/4, and immune-related adverse events (irAEs) were 89.5%, 41.2%, and 27.2%, respectively. 17 (11.8%) pts had treatment-associated hypothyroidism, and 12 (8.3%) cases reported secondary adrenal insufficiency/hypophysitis (SAI). No specific statistical associations were observed between specific subgroups and the incidence of irAEs, except for SAI. SAI was associated with younger patient age, with median ages of 38 [IQR 33.5-40.8] and 46 [38-56], for patients with and without a diagnosis of SAI, respectively (p=0.012).

Conclusions

In our real-world cohort, the incidence of secondary adrenal insufficiency/hypophysitis was higher than the reported results of the pivotal clinical trial. An interesting correlation was evidenced between patient age and this particular irAE. We anticipate that our discoveries will enhance recognition of this particular side effect. Additional research is required to assess the long-term impact of this irAE on quality of life.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.