3MO - Efficacy of neoadjuvant pembrolizuamb in early triple-negative breast cancer according to germline BRCA-1/2 mutation

Background

The KEYNOTE-522 trial demonstrated that adding pembrolizumab to neoadjuvant chemotherapy enhances pathologic complete response (pCR) and survival outcomes in early-stage triple-negative breast cancer (TNBC). However, the predictive value of biomarkers, including PD-L1, for pembrolizumab efficacy remains unclear. This study explored whether germline BRCA (gBRCA)-1/2 mutations can serve as potential biomarkers for pembrolizumab efficacy.

Methods

We included 199 TNBC patients who received neoadjuvant chemotherapy and had gBRCA-1/2 mutation test at initial diagnosis. All patients underwent four cycles of carboplatin (AUC 5 or 6) every 3 weeks with twelve weekly cycles of paclitaxel, followed by four cycles of anthracycline plus cyclophosphamide every 3 weeks. This neoadjuvant chemotherapy regimen was administered with or without eight cycles of pembrolizumab (200 mg) every 3 weeks. pCR rates were assessed according to administration of pembrolizumab stratified by gBRCA-1/2 mutation status. pCR was defined as the absence of invasive cancer in the breast and axillary lymph nodes (ypT0/is, ypN0).

Results

Of the 199 patients, 89 (44.7%) received pembrolizumab with neoadjuvant chemotherapy, and 49 (24.6%) had gBRCA-1/2 mutations. Although not statistically significant, pCR rates were higher in the pembrolizumab group compared to the non-pembrolizumab group (67.4% vs. 59.1%, p = 0.227) and in patients with gBRCA-1/2 mutations compared to those without (73.5% vs. 59.3%, p = 0.075). In the gBRCA wild-type cohort (n = 150), pCR rates were 55.1% (43 of 78) for the non-pembrolizumab group and 63.9% (46 of 72) for the pembrolizumab group (p = 0.275). Among patients with gBRCA-1/2 mutations (n = 49), pCR rates were 68.8% (22 of 32) without pembrolizumab and 82.4% (14 of 17) with pembrolizumab (p = 0.305).

Conclusions

Similar to PD-L1, the presence of gBRCA-1/2 mutations was associated with increased pCR rates in both the pembrolizumab and non-pembrolizumab groups, suggesting that gBRCA-1/2 mutation is not a suitable biomarker for predicting pembrolizumab efficacy. Further translational research with larger cohorts is necessary to identify novel predictive biomarkers for pembrolizumab response.

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.