Atezolizumab and nab-Paclitaxel in Advanced Triple-Negative Breast Cancer: Biomarker Evaluation of the IMpassion130 Study

Emens, LA; Molinero, L; Loi, S; Rugo, HS; Schneeweiss, A; Dieras, V; Iwata, H; Barrios, CH; Nechaeva, M; Nguyen-Duc, A; Chui, SY; Husain, A; Winer, EP; Adams, S; Schmid, P

Author(s): Emens, LA; Molinero, L; Loi, S; Rugo, HS; Schneeweiss, A; Dieras, V; Iwata, H; Barrios, CH; Nechaeva, M; Nguyen-Duc, A; Chui, SY; Husain, A; Winer, EP; Adams, S; Schmid, P;
Details: Publication Year 2021-08,Volume 113,Issue #8,Page 1005-1016
Journal Title: Journal of the National Cancer Institute
Publication Type: Research article
Abstract: BACKGROUND: Understanding the impact of the tumor immune microenvironment and BRCA1/2-related DNA repair deficiencies on the clinical activity of immune checkpoint inhibitors may help optimize both patient and treatment selection in metastatic triple-negative breast cancer. In this substudy from the phase 3 IMpassion130 trial, immune biomarkers and BRCA1/2 alterations were evaluated for association with clinical benefit with atezolizumab and nab-paclitaxel (A+nP) vs placebo and nP in unresectable (P+nP) locally advanced or metastatic triple-negative breast cancer. METHODS: Patients were randomly assigned 1:1 to nab-paclitaxel 100 mg/m2 (days 1, 8, and 15 of a 28-day cycle) and atezolizumab 840 mg every 2 weeks or placebo until progression or toxicity. Progression-free survival and overall survival were evaluated based on programmed death-ligand 1 (PD-L1) expression on immune cells (IC) and tumor cells, intratumoral CD8, stromal tumor-infiltrating lymphocytes, and BRCA1/2 mutations. RESULTS: PD-L1 IC+ in either primary or metastatic tumor tissue was linked to progression-free survival and overall survival benefit with A+nP. PD-L1 IC+ low (26.9%; 243 of 902 patients) and high (13.9%; 125 of 902 patients) populations had improved outcomes that were comparable. Intratumoral CD8 and stromal tumor-infiltrating lymphocytes positivity (sTIL+) were associated with PD-L1 IC+ status; improved outcomes were observed with A+nP vs P+nP only in CD8+ and sTIL+ patients who were also PD-L1 IC+. BRCA1/2 mutations (occurring in 14.5% [89 of 612 patients]) were not associated with PD-L1 IC status, and PD-L1 IC+ patients benefited from A+nP regardless of BRCA1/2 mutation status. CONCLUSIONS: Although A+nP was more efficacious in patients with richer tumor immune microenvironment, clinical benefit was only observed in patients whose tumors were PD-L1 IC+.
Keywords: Albumins; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; B7-H1 Antigen/metabolism; Biomarkers; Humans; Lymphocytes, Tumor-Infiltrating/pathology; Paclitaxel; *Triple Negative Breast Neoplasms/pathology; Tumor Microenvironment
Department(s): Laboratory Research; Medical Oncology
PubMed ID: 33523233
Publisher's Version: https://doi.org/10.1093/jnci/djab004
Open Access at Publisher's Site: https://doi.org/10.1093/jnci/djab004
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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