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

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Julia Foldi, Andrea Silber, Emily Reisenbichler, Kamaljeet Singh, Neal Fischbach, Justin Persico, Kerin Adelson, Anamika Katoch, Nina Horowitz, Donald Lannin, Anees Chagpar, Tristen Park, Michal Marczyk, Courtney Frederick, Trisha Burrello, Eiman Ibrahim, Tao Qing, Yalai Bai, Kim Blenman, David L. Rimm, Lajos Pusztai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a0cd120873bd4d7189d5d75f4bae0e84
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a0cd120873bd4d7189d5d75f4bae0e84
record_format	dspace
spelling	oai:doaj.org-article:a0cd120873bd4d7189d5d75f4bae0e842021-12-02T14:11:05ZNeoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer10.1038/s41523-021-00219-72374-4677https://doaj.org/article/a0cd120873bd4d7189d5d75f4bae0e842021-02-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00219-7https://doaj.org/toc/2374-4677Abstract 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.Julia FoldiAndrea SilberEmily ReisenbichlerKamaljeet SinghNeal FischbachJustin PersicoKerin AdelsonAnamika KatochNina HorowitzDonald LanninAnees ChagparTristen ParkMichal MarczykCourtney FrederickTrisha BurrelloEiman IbrahimTao QingYalai BaiKim BlenmanDavid L. RimmLajos PusztaiNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Julia Foldi Andrea Silber Emily Reisenbichler Kamaljeet Singh Neal Fischbach Justin Persico Kerin Adelson Anamika Katoch Nina Horowitz Donald Lannin Anees Chagpar Tristen Park Michal Marczyk Courtney Frederick Trisha Burrello Eiman Ibrahim Tao Qing Yalai Bai Kim Blenman David L. Rimm Lajos Pusztai Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer
description	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.
format	article
author	Julia Foldi Andrea Silber Emily Reisenbichler Kamaljeet Singh Neal Fischbach Justin Persico Kerin Adelson Anamika Katoch Nina Horowitz Donald Lannin Anees Chagpar Tristen Park Michal Marczyk Courtney Frederick Trisha Burrello Eiman Ibrahim Tao Qing Yalai Bai Kim Blenman David L. Rimm Lajos Pusztai
author_facet	Julia Foldi Andrea Silber Emily Reisenbichler Kamaljeet Singh Neal Fischbach Justin Persico Kerin Adelson Anamika Katoch Nina Horowitz Donald Lannin Anees Chagpar Tristen Park Michal Marczyk Courtney Frederick Trisha Burrello Eiman Ibrahim Tao Qing Yalai Bai Kim Blenman David L. Rimm Lajos Pusztai
author_sort	Julia Foldi
title	Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer
title_short	Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer
title_full	Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer
title_fullStr	Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer
title_full_unstemmed	Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer
title_sort	neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a0cd120873bd4d7189d5d75f4bae0e84
work_keys_str_mv	AT juliafoldi neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT andreasilber neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT emilyreisenbichler neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT kamaljeetsingh neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT nealfischbach neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT justinpersico neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT kerinadelson neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT anamikakatoch neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT ninahorowitz neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT donaldlannin neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT aneeschagpar neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT tristenpark neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT michalmarczyk neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT courtneyfrederick neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT trishaburrello neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT eimanibrahim neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT taoqing neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT yalaibai neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT kimblenman neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT davidlrimm neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer AT lajospusztai neoadjuvantdurvalumabplusweeklynabpaclitaxelanddosedensedoxorubicincyclophosphamideintriplenegativebreastcancer
_version_	1718391860069662720

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

Ejemplares similares