TY - JOUR
T1 - Current Landscape of Immunotherapy in Breast Cancer
T2 - A Review
AU - Adams, Sylvia
AU - Gatti-Mays, Margaret E.
AU - Kalinsky, Kevin
AU - Korde, Larissa A.
AU - Sharon, Elad
AU - Amiri-Kordestani, Laleh
AU - Bear, Harry
AU - McArthur, Heather L.
AU - Frank, Elizabeth
AU - Perlmutter, Jane
AU - Page, David B.
AU - Vincent, Benjamin
AU - Hayes, Jennifer F.
AU - Gulley, James L.
AU - Litton, Jennifer K.
AU - Hortobagyi, Gabriel N.
AU - Chia, Stephen
AU - Krop, Ian
AU - White, Julia
AU - Sparano, Joseph
AU - Disis, Mary L.
AU - Mittendorf, Elizabeth Ann
N1 - Funding Information:
institutional research funding from Merck, Genentech, Celgene, and Amgen during the conduct of the study. Dr Kalinsky reported personal fees from Biotheranostics, Eli Lilly, Pfizer, Ipsen, and Novartis, stock ownership in Novartis, and spouse employed by Novartis and Array Biopharma, all outside the submitted work. Dr Bear reported grants and personal fees from Merck during the conduct of the study and grants and personal fees from Genomic Health Inc, outside the submitted work. Dr McArthur reported grants, personal fees, and nonfinancial support from Merck, nonfinancial support from Bristol-Myers Squibb, grants and nonfinancial support from MedImmune/Astra Zeneca, and personal fees from Roche/Genentech, Lilly, Peregrine Pharmaceuticals, TapImmune Inc, Amgen, Puma, Pfizer, Immunomedics, Syndax, Genomic Health, Spectrum Pharmaceuticals, OBI Pharma, Calithera Biosciences, and Celgene during the conduct of the study. Dr Page reported grants, personal fees, and nonfinancial support from Merck and Bristol-Myers Squibb, personal fees and nonfinancial support from Genentech, Nektar, Novartis, Syndax, and Myriad Genetics, grants from MedImmune, and personal fees from Nanostring during the conduct of the study. Dr Vincent reported grants from Merck during the conduct of the study and serving as Scientific Advisory Board Member for Nanostring Inc. Dr Gulley reported that the National Cancer Institutes has several Cooperative Research and Development Agreements (CRADAs) with various biotech and pharma agencies involved in immunotherapy. Dr Litton reported grants from Pfizer, EMD Serono, Genentech, Novartis, GlaxoSmithKline, Astra Zeneca, and Medivation outside the submitted work. Dr Hortobagyi reported personal fees from Novartis outside the submitted work. Dr Chia reported personal fees from Hoffmann LaRoche, Novartis, and Pfizer and grants from Hoffmann LaRoche, Genentech, and BMS during the conduct of the study; and personal fees from Novartis, Pfizer, and Eli Lilly outside the submitted work. Dr Krop reported grants and personal fees from Genentech/Roche and personal fees from Daiichi/Sankyo, Macrogenics, and Taiho outside the submitted work. Dr Sparano reported personal fees, consultancy, and study participation from Roche and personal fees and consultancy Astra Zeneca during the conduct of the study. Dr Disis reported Janssen, Celgene, Pfizer, EMD Serono, EpiThany, and Silverback Therapeutics during the conduct of the study; in addition, Dr Disis had a patent issued, associated with University of Washington. Dr Mittendorf reported funding for a clinical trial for which she was principal investigator from Astra Zeneca, EMD Serono, Galena Biopharma, and Genentech/Roche, and personal fees from Genentech/Roche, Merck, Peregrine Pharmaceuticals, SELLAS Life Sciences, and Tapimmune Inc during the conduct of the study; and personal fees from Physician Education Resource outside the submitted work. No other disclosures were reported.
Publisher Copyright:
© 2019 American Medical Association. All rights reserved.
PY - 2019/8
Y1 - 2019/8
N2 - Importance: There is tremendous interest in using immunotherapy to treat breast cancer, as evidenced by the more than 290 clinical trials ongoing at the time of this narrative review. The objective of this review is to describe the current status of immunotherapy in breast cancer, highlighting its potential in both early-stage and metastatic disease. Observations: After searching ClinicalTrials.gov on April 24, 2018, and PubMed up to June 30, 2018, to identify breast cancer immunotherapy trials, we found that immune checkpoint blockade (ICB) is the most investigated form of immunotherapy in breast cancer. Use of ICB as monotherapy has achieved objective responses in patients with breast cancer, with higher rates seen when administered in earlier lines of therapy. For responding patients, those responses are durable. More recent data suggest clinical efficacy when ICB is given in combination with chemotherapy. Ongoing studies are evaluating combination strategies pairing ICB with additional chemotherapeutic agents, targeted therapy, vaccines, and local ablative therapies to enhance response. To date, robust predictive biomarkers for response to ICB have not been established. Conclusions and Relevance: It is anticipated that combination therapy strategies will be the way forward for immunotherapy in breast cancer, with an improved understanding of tumor, microenvironment, and host factors informing treatment combination decisions. Thoughtful study design incorporating appropriate end points and correlative studies will be critical in identifying optimal strategies for enhancing the immune response against breast tumors.
AB - Importance: There is tremendous interest in using immunotherapy to treat breast cancer, as evidenced by the more than 290 clinical trials ongoing at the time of this narrative review. The objective of this review is to describe the current status of immunotherapy in breast cancer, highlighting its potential in both early-stage and metastatic disease. Observations: After searching ClinicalTrials.gov on April 24, 2018, and PubMed up to June 30, 2018, to identify breast cancer immunotherapy trials, we found that immune checkpoint blockade (ICB) is the most investigated form of immunotherapy in breast cancer. Use of ICB as monotherapy has achieved objective responses in patients with breast cancer, with higher rates seen when administered in earlier lines of therapy. For responding patients, those responses are durable. More recent data suggest clinical efficacy when ICB is given in combination with chemotherapy. Ongoing studies are evaluating combination strategies pairing ICB with additional chemotherapeutic agents, targeted therapy, vaccines, and local ablative therapies to enhance response. To date, robust predictive biomarkers for response to ICB have not been established. Conclusions and Relevance: It is anticipated that combination therapy strategies will be the way forward for immunotherapy in breast cancer, with an improved understanding of tumor, microenvironment, and host factors informing treatment combination decisions. Thoughtful study design incorporating appropriate end points and correlative studies will be critical in identifying optimal strategies for enhancing the immune response against breast tumors.
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U2 - 10.1001/jamaoncol.2018.7147
DO - 10.1001/jamaoncol.2018.7147
M3 - Review article
C2 - 30973611
AN - SCOPUS:85064259674
SN - 2374-2437
VL - 5
SP - 1205
EP - 1214
JO - JAMA Oncology
JF - JAMA Oncology
IS - 8
ER -