SP142 PD-L1 Assays in Multiple Samples from the Same Patients with Early or Advanced Triple-Negative Breast Cancer

SIMPLE SUMMARY: The IMpassion130 trial suggests that metastatic triple-negative breast cancer (TNBC) patients with PD-L1+ derived a clinical benefit from atezolizumab-combined treatment regardless of the sample collection time or origin. Therefore, if the PD-L1 test is positive at least once in multiple samples, the patient could have an opportunity to receive atezolizumab-based treatments. We aimed to know whether multiple PD-L1 testing might increase a rate of PD-L1+ in patients with TNBC. SP142 PD-L1 assays were performed in multiple samples from 77 patients in early TNBC. Multiple PD-L1 test using multiple samples raised the PD-L1+ rate more than a single biopsied sample test (68.8% vs. 37.6%, p = 0.00002). Among the group with metastatic TNBC treated with atezolizumab and nab-paclitaxel, PD-L1 assays were performed at least twice in 8/12 patients; 5/8 had heterogeneous results of PD-L1 assays. Consequently, a vigorous PD-L1 test using multiple samples was considered necessary in TNBC because a single test might be insufficient to represent the PD-L1 status. ABSTRACT: Purpose: The discernible PD-L1 staining of tumor-infiltrating lymphocytes occupying ≥ 1% of the tumor area is considered SP142 PD-L1 positive for atezolizumab, and the PD-L1 status of multiple samples within a single patient could be discrepant. In this study, we evaluated the PD-L1 status by using the SP142 clone in serially collected matched samples from the same individuals with early or metastatic triple-negative breast cancer (TNBC). Method: the SP142 PD-L1 assay was performed using biopsies and surgical specimens from 77 patients with early TNBC. Among these patients, 47 underwent upfront surgery, and 30 underwent neoadjuvant chemotherapy (NAC) between biopsy and surgery. PD-L1 assays were performed at least twice in 8/12 (66.7%) patients with metastatic TNBC treated with atezolizumab and nab-paclitaxel. Results: Of the 47 patients who underwent upfront surgery, 15/47 (31.9%) had PD-L1+ on biopsied samples. PD-L1+ rates in the biopsy and surgical specimens increased to 66.0% (33 of 47) after subsequent surgery. Similarly, in the 30 patients with residual invasive cancer who underwent neoadjuvant chemotherapy, the PD-L1+ rate increased from 46.6% at baseline to 74.2% after surgery. In the 77 patients with early TNBC, multiple PD-L1 testing in the biopsies and surgical specimens significantly increased the number of patients with PD-L1+ compared with the number of patients with PD-L1+ assessed with initial biopsy samples alone (68.8% vs. 37.6%; p = 0.00002). Among the metastatic TNBC patients, those with constant PD-L1+ over 1% positivity in multiple samples showed a response which was longer than 12 months. Conclusions: Our findings reveal the heterogeneous SP142 PD-L1 expression in TNBC and suggest that PD-L1 evaluation in baseline biopsy might be insufficient to represent the PD-L1 status of whole tumors. In TNBC, vigorous PD-L1 examination using multiple available tumor samples could identify more patients eligible for immune checkpoint blockade.