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A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer
PURPOSE: Neoadjuvant combination immune checkpoint blockade and intralesional oncolytic virotherapy have the potential to activate antitumor responses in patients with breast cancer. EXPERIMENTAL DESIGN: Eligibility for this pilot phase I trial included patients with localized HER2-negative breast c...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for Cancer Research
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10445661/ https://www.ncbi.nlm.nih.gov/pubmed/37621406 http://dx.doi.org/10.1158/2767-9764.CRC-23-0145 |
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author | Nguyen, Vina P. Campbell, Katie M. Nowicki, Theodore S. Elumalai, Nila Medina, Egmidio Baselga-Carretero, Ignacio DiNome, Maggie L. Chang, Helena R. Oseguera, Denise K. Ribas, Antoni Glaspy, John A. |
author_facet | Nguyen, Vina P. Campbell, Katie M. Nowicki, Theodore S. Elumalai, Nila Medina, Egmidio Baselga-Carretero, Ignacio DiNome, Maggie L. Chang, Helena R. Oseguera, Denise K. Ribas, Antoni Glaspy, John A. |
author_sort | Nguyen, Vina P. |
collection | PubMed |
description | PURPOSE: Neoadjuvant combination immune checkpoint blockade and intralesional oncolytic virotherapy have the potential to activate antitumor responses in patients with breast cancer. EXPERIMENTAL DESIGN: Eligibility for this pilot phase I trial included patients with localized HER2-negative breast cancer who received systemic nivolumab and ipilimumab and intratumor talimogene laherparepvec (T-VEC; NCT04185311). The primary objective was to evaluate the safety and adverse event profile of immunotherapy combined with T-VEC in patients with localized, HER2-negative breast cancer. RESULTS: Six patients were enrolled, 4 having relapses after prior neoadjuvant chemotherapy and 2 who were previously untreated. Toxicities included 1 patient having grade 3 hypotension and type 1 diabetes mellitus, 3 patients with hypothyroidism, and all patients having constitutional symptoms known to be associated with the administration of T-VEC. One patient had a pathologic complete response, 3 patients had pathologic partial responses, 1 showed no significant response, and 1 had disease progression. Biopsies demonstrated increased immune cell infiltration in samples from patients who responded to therapy. CONCLUSIONS: This triple immunotherapy regimen provided responses in patients with advanced or relapsed HER2-negative breast cancer, at the expense of long-term toxicities. SIGNIFICANCE: Systemic immune checkpoint blockade with a programmed death receptor 1 and a CTL antigen-4 blocking antibody, combined with intralesional oncolytic virotherapy, is a chemotherapy-free combination aimed at inducing an antitumor immune response locally and systemic immunity. |
format | Online Article Text |
id | pubmed-10445661 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for Cancer Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-104456612023-08-24 A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer Nguyen, Vina P. Campbell, Katie M. Nowicki, Theodore S. Elumalai, Nila Medina, Egmidio Baselga-Carretero, Ignacio DiNome, Maggie L. Chang, Helena R. Oseguera, Denise K. Ribas, Antoni Glaspy, John A. Cancer Res Commun Research Article PURPOSE: Neoadjuvant combination immune checkpoint blockade and intralesional oncolytic virotherapy have the potential to activate antitumor responses in patients with breast cancer. EXPERIMENTAL DESIGN: Eligibility for this pilot phase I trial included patients with localized HER2-negative breast cancer who received systemic nivolumab and ipilimumab and intratumor talimogene laherparepvec (T-VEC; NCT04185311). The primary objective was to evaluate the safety and adverse event profile of immunotherapy combined with T-VEC in patients with localized, HER2-negative breast cancer. RESULTS: Six patients were enrolled, 4 having relapses after prior neoadjuvant chemotherapy and 2 who were previously untreated. Toxicities included 1 patient having grade 3 hypotension and type 1 diabetes mellitus, 3 patients with hypothyroidism, and all patients having constitutional symptoms known to be associated with the administration of T-VEC. One patient had a pathologic complete response, 3 patients had pathologic partial responses, 1 showed no significant response, and 1 had disease progression. Biopsies demonstrated increased immune cell infiltration in samples from patients who responded to therapy. CONCLUSIONS: This triple immunotherapy regimen provided responses in patients with advanced or relapsed HER2-negative breast cancer, at the expense of long-term toxicities. SIGNIFICANCE: Systemic immune checkpoint blockade with a programmed death receptor 1 and a CTL antigen-4 blocking antibody, combined with intralesional oncolytic virotherapy, is a chemotherapy-free combination aimed at inducing an antitumor immune response locally and systemic immunity. American Association for Cancer Research 2023-08-23 /pmc/articles/PMC10445661/ /pubmed/37621406 http://dx.doi.org/10.1158/2767-9764.CRC-23-0145 Text en © 2023 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by/4.0/This open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license. |
spellingShingle | Research Article Nguyen, Vina P. Campbell, Katie M. Nowicki, Theodore S. Elumalai, Nila Medina, Egmidio Baselga-Carretero, Ignacio DiNome, Maggie L. Chang, Helena R. Oseguera, Denise K. Ribas, Antoni Glaspy, John A. A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer |
title | A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer |
title_full | A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer |
title_fullStr | A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer |
title_full_unstemmed | A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer |
title_short | A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer |
title_sort | pilot study of neoadjuvant nivolumab, ipilimumab, and intralesional oncolytic virotherapy for her2-negative breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10445661/ https://www.ncbi.nlm.nih.gov/pubmed/37621406 http://dx.doi.org/10.1158/2767-9764.CRC-23-0145 |
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