Association between pembrolizumab-related thyroid adverse events and outcomes in early-stage triple negative breast cancer patients

Pembrolizumab-related thyroid dysfunction has been associated with better outcomes in metastatic cancer patients. This study aims to examine the outcomes [pathological Complete Response (pCR) and event-free survival (EFS)] in early-stage triple negative breast cancer (TNBC) patients receiving preoperative therapy who developed pembrolizumab-related thyroid dysfunction. Patients were divided into four groups based on the occurrence or not of pembrolizumab-related thyroid dysfunction (group A and D, respectively) and, in case of pre-existing thyroid disorder, based on the need of levothyroxine start/adjustment or not (group B and C, respectively). pCR and EFS in groups ABC were compared to the ones in group D. Sixty-four early-stage TNBC patients were included and the median follow-up was 16.5 months (IQR 12.0-23.8). Multiple patterns of thyroid irAEs were observed (overt hypothyroidism in 56.3%, subclinical thyrotoxicosis in 28.1%, overt thyrotoxicosis and subclinical hypothyroidism in 21.9%, and 21.9% of patients). No statistical difference was found in pCR (chi-square test, p=0.611) comparing groups ABC to group D. The median EFS in groups ABC and in group D were 16.5 (IQR 12.0-24.0) and 16.0 (IQR 12.0–22.3) months, respectively (log-rank test, p=0.671). The percentage of patients obtaining pCR was 85.7% in patients developing pembrolizumab–related overt thyrotoxicosis and 42.1% in remaining patients (Chi-square test, p=0.036). The EFS was 16.0 months (IQR 12.0-25.0) in patients developing pembrolizumab–related overt thyrotoxicosis and 16.0 months (IQR 12.0-23.5) in the remaining patients (log-rank test, p=0.494). In conclusion, multiple patterns of pembrolizumab-related thyroid dysfunction occurs in early-stage TNBC. Patients developing pembrolizumab-related overt thyrotoxicosis are more likely to achieve pCR.