Predictors of pathologic complete response in early-stage triple-negative breast cancer treated with neoadjuvant...

The KEYNOTE-522 clinical trial demonstrated that the addition of pembrolizumab to 8 cycles of neoadjuvant chemotherapy (NAC) improves pathologic complete response (pCR) rates and overall survival in early-stage triple-negative breast cancer (TNBC). However, predictors of response and the benefit of alternative NAC backbones with immunotherapy are not known. This multi-institutional study evaluates clinical factors and treatment variables associated with pCR following NAC plus pembrolizumab in a diverse, real-world cohort.

This multi-institution retrospective study analyzed patients with early-stage TNBC diagnosed between July 1, 2021, and December 31, 2023, across three hospital systems. Eligible patients received at least one cycle of NAC and pembrolizumab. Predictors of pCR were assessed using logistic regression.

Of the 374 patients included, the pCR rate was 61.2%. The cohort was racially and ethnically diverse, with 29.1% of patients identifying as non-White. Almost half (48.4%) had a BMI ≥30, and 70 patients (18.7%) had pre-existing diabetes mellitus. Approximately two-thirds (64.4%) completed 8 cycles of neoadjuvant pembrolizumab, while 72.5% completed 8 cycles of NAC. On univariate analysis, age less than 55 years (p = 0.03), absence of diabetes mellitus (p = 0.03), high tumor grade (p = 0.005), the completion of 8 or more cycles of neoadjuvant pembrolizumab (p = 0.04) and 8 cycles of NAC (p = 0.03) were associated with pCR. There was a trend towards higher pCR rates with the receipt of at least one cycle of anthracycline-cyclophosphamide (p = 0.07). Lack of diabetes mellitus (p = 0.03) and high tumor grade (p = 0.004) remained significant on multivariate analysis.

This study supports the use of KEYNOTE-522 in a diverse, real-world population of patients with early-stage TNBC. Patients with diabetes were less likely to achieve a pCR, suggesting a potential impact of glucose metabolism on chemo-immunotherapy resistance.