Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer

Julia Foldi, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.Follow
Andrea Silber, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.Follow
Emily Reisenbichler, Department of Pathology, Yale School of Medicine, New Haven, CT, USA.Follow
Kamaljeet Singh, Department of Pathology, Yale School of Medicine, New Haven, CT, USA.Follow
Neal Fischbach, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.Follow
Justin Persico, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.Follow
Kerin Adelson, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.
Anamika Katoch, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.Follow
Nina Horowitz, Department of Surgery, Yale School of Medicine, New Haven, CT, USA.
Donald Lannin, Department of Surgery, Yale School of Medicine, New Haven, CT, USA.
Anees Chagpar, Department of Surgery, Yale School of Medicine, New Haven, CT, USA.Follow
Tristen Park, Department of Surgery, Yale School of Medicine, New Haven, CT, USA.Follow
Michal Marczyk, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.
Courtney Frederick, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.Follow
Trisha Burrello, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.
Eiman Ibrahim, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.
Tao Qing, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.Follow
Yalai Bai, Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
Kim Blenman, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.Follow
David L. Rimm, Department of Pathology, Yale School of Medicine, New Haven, CT, USA.Follow
Lajos Pusztai, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA. lajos.pusztai@yale.edu.Follow

Document Type

Article

Publication Title

NPJ breast cancer

Abstract

The goal of this Phase I/II trial is to assess the safety and efficacy of administering durvalumab concurrent with weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide (ddAC) neoadjuvant therapy for stages I-III triple-negative breast cancer. The primary endpoint is pathologic complete response (pCR:ypT0/is, ypN0). The response was correlated with PDL1 expression and stromal tumor-infiltrating lymphocytes (sTILs). Two dose levels of durvalumab (3 and 10 mg/kg) were assessed. PD-L1 was assessed using the SP263 antibody; ≥1% immune and tumor cell staining was considered positive; sTILs were calculated as the area occupied by mononuclear inflammatory cells over the total intratumoral stromal area. 59 patients were evaluable for toxicity and 55 for efficacy in the Phase II study (10 mg/kg dose). No dose-limiting toxicities were observed in Phase I. In Phase II, pCR rate was 44% (95% CI: 30-57%); 18 patients (31%) experienced grade 3/4 treatment-related adverse events (AE), most frequently neutropenia (n = 4) and anemia (n = 4). Immune-related grade 3/4 AEs included Guillain-Barre syndrome (n = 1), colitis (n = 2), and hyperglycemia (n = 2). Of the 50 evaluable patients for PD-L1, 31 (62%) were PD-L1 positive. pCR rates were 55% (95% CI: 0.38-0.71) and 32% (95% CI: 0.12-0.56) in the PD-L1 positive and negative groups (p = 0.15), respectively. sTIL counts were available on 52 patients and were significantly higher in the pCR group (p = 0.0167). Concomitant administration of durvalumab with sequential weekly nab-paclitaxel and ddAC neoadjuvant chemotherapy resulted in a pCR rate of 44%; pCR rates were higher in sTIL-high cancers.

First Page

9

DOI

10.1038/s41523-021-00219-7

Publication Date

2-8-2021

Identifier

33558513 (pubmed); PMC7870853 (pmc); 10.1038/s41523-021-00219-7 (doi); 10.1038/s41523-021-00219-7 (pii)

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