Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study

Treatment options for previously treated metastatic triple-negative breast cancer (mTNBC) are limited. In cohort A of the phase II KEYNOTE-086 study, we evaluated pembrolizumab as second or later line of treatment for patients with mTNBC. Eligible patients had centrally confirmed mTNBC, ≥1 systemic...

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Published in:Annals of oncology Vol. 30; no. 3; p. 397
Main Authors: Adams, S, Schmid, P, Rugo, H S, Winer, E P, Loirat, D, Awada, A, Cescon, D W, Iwata, H, Campone, M, Nanda, R, Hui, R, Curigliano, G, Toppmeyer, D, O'Shaughnessy, J, Loi, S, Paluch-Shimon, S, Tan, A R, Card, D, Zhao, J, Karantza, V, Cortés, J
Format: Journal Article
Language:English
Published: England 01.03.2019
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ISSN:1569-8041, 1569-8041
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Abstract Treatment options for previously treated metastatic triple-negative breast cancer (mTNBC) are limited. In cohort A of the phase II KEYNOTE-086 study, we evaluated pembrolizumab as second or later line of treatment for patients with mTNBC. Eligible patients had centrally confirmed mTNBC, ≥1 systemic therapy for metastatic disease, prior treatment with anthracycline and taxane in any disease setting, and progression on or after the most recent therapy. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. Primary end points were objective response rate in the total and PD-L1-positive populations, and safety. Secondary end points included duration of response, disease control rate (percentage of patients with complete or partial response or stable disease for ≥24 weeks), progression-free survival, and overall survival. All enrolled patients (N = 170) were women, 61.8% had PD-L1-positive tumors, and 43.5% had received ≥3 previous lines of therapy for metastatic disease. ORR (95% CI) was 5.3% (2.7-9.9) in the total and 5.7% (2.4-12.2) in the PD-L1-positive populations. Disease control rate (95% CI) was 7.6% (4.4-12.7) and 9.5% (5.1-16.8), respectively. Median duration of response was not reached in the total (range, 1.2+-21.5+) and in the PD-L1-positive (range, 6.3-21.5+) populations. Median PFS was 2.0 months (95% CI, 1.9-2.0), and the 6-month rate was 14.9%. Median OS was 9.0 months (95% CI, 7.6-11.2), and the 6-month rate was 69.1%. Treatment-related adverse events occurred in 103 (60.6%) patients, including 22 (12.9%) with grade 3 or 4 AEs. There were no deaths due to AEs. Pembrolizumab monotherapy demonstrated durable antitumor activity in a subset of patients with previously treated mTNBC and had a manageable safety profile. ClinicalTrials.gov, NCT02447003.
AbstractList Treatment options for previously treated metastatic triple-negative breast cancer (mTNBC) are limited. In cohort A of the phase II KEYNOTE-086 study, we evaluated pembrolizumab as second or later line of treatment for patients with mTNBC. Eligible patients had centrally confirmed mTNBC, ≥1 systemic therapy for metastatic disease, prior treatment with anthracycline and taxane in any disease setting, and progression on or after the most recent therapy. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. Primary end points were objective response rate in the total and PD-L1-positive populations, and safety. Secondary end points included duration of response, disease control rate (percentage of patients with complete or partial response or stable disease for ≥24 weeks), progression-free survival, and overall survival. All enrolled patients (N = 170) were women, 61.8% had PD-L1-positive tumors, and 43.5% had received ≥3 previous lines of therapy for metastatic disease. ORR (95% CI) was 5.3% (2.7-9.9) in the total and 5.7% (2.4-12.2) in the PD-L1-positive populations. Disease control rate (95% CI) was 7.6% (4.4-12.7) and 9.5% (5.1-16.8), respectively. Median duration of response was not reached in the total (range, 1.2+-21.5+) and in the PD-L1-positive (range, 6.3-21.5+) populations. Median PFS was 2.0 months (95% CI, 1.9-2.0), and the 6-month rate was 14.9%. Median OS was 9.0 months (95% CI, 7.6-11.2), and the 6-month rate was 69.1%. Treatment-related adverse events occurred in 103 (60.6%) patients, including 22 (12.9%) with grade 3 or 4 AEs. There were no deaths due to AEs. Pembrolizumab monotherapy demonstrated durable antitumor activity in a subset of patients with previously treated mTNBC and had a manageable safety profile. ClinicalTrials.gov, NCT02447003.
Treatment options for previously treated metastatic triple-negative breast cancer (mTNBC) are limited. In cohort A of the phase II KEYNOTE-086 study, we evaluated pembrolizumab as second or later line of treatment for patients with mTNBC.BACKGROUNDTreatment options for previously treated metastatic triple-negative breast cancer (mTNBC) are limited. In cohort A of the phase II KEYNOTE-086 study, we evaluated pembrolizumab as second or later line of treatment for patients with mTNBC.Eligible patients had centrally confirmed mTNBC, ≥1 systemic therapy for metastatic disease, prior treatment with anthracycline and taxane in any disease setting, and progression on or after the most recent therapy. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. Primary end points were objective response rate in the total and PD-L1-positive populations, and safety. Secondary end points included duration of response, disease control rate (percentage of patients with complete or partial response or stable disease for ≥24 weeks), progression-free survival, and overall survival.PATIENTS AND METHODSEligible patients had centrally confirmed mTNBC, ≥1 systemic therapy for metastatic disease, prior treatment with anthracycline and taxane in any disease setting, and progression on or after the most recent therapy. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. Primary end points were objective response rate in the total and PD-L1-positive populations, and safety. Secondary end points included duration of response, disease control rate (percentage of patients with complete or partial response or stable disease for ≥24 weeks), progression-free survival, and overall survival.All enrolled patients (N = 170) were women, 61.8% had PD-L1-positive tumors, and 43.5% had received ≥3 previous lines of therapy for metastatic disease. ORR (95% CI) was 5.3% (2.7-9.9) in the total and 5.7% (2.4-12.2) in the PD-L1-positive populations. Disease control rate (95% CI) was 7.6% (4.4-12.7) and 9.5% (5.1-16.8), respectively. Median duration of response was not reached in the total (range, 1.2+-21.5+) and in the PD-L1-positive (range, 6.3-21.5+) populations. Median PFS was 2.0 months (95% CI, 1.9-2.0), and the 6-month rate was 14.9%. Median OS was 9.0 months (95% CI, 7.6-11.2), and the 6-month rate was 69.1%. Treatment-related adverse events occurred in 103 (60.6%) patients, including 22 (12.9%) with grade 3 or 4 AEs. There were no deaths due to AEs.RESULTSAll enrolled patients (N = 170) were women, 61.8% had PD-L1-positive tumors, and 43.5% had received ≥3 previous lines of therapy for metastatic disease. ORR (95% CI) was 5.3% (2.7-9.9) in the total and 5.7% (2.4-12.2) in the PD-L1-positive populations. Disease control rate (95% CI) was 7.6% (4.4-12.7) and 9.5% (5.1-16.8), respectively. Median duration of response was not reached in the total (range, 1.2+-21.5+) and in the PD-L1-positive (range, 6.3-21.5+) populations. Median PFS was 2.0 months (95% CI, 1.9-2.0), and the 6-month rate was 14.9%. Median OS was 9.0 months (95% CI, 7.6-11.2), and the 6-month rate was 69.1%. Treatment-related adverse events occurred in 103 (60.6%) patients, including 22 (12.9%) with grade 3 or 4 AEs. There were no deaths due to AEs.Pembrolizumab monotherapy demonstrated durable antitumor activity in a subset of patients with previously treated mTNBC and had a manageable safety profile.CONCLUSIONSPembrolizumab monotherapy demonstrated durable antitumor activity in a subset of patients with previously treated mTNBC and had a manageable safety profile.ClinicalTrials.gov, NCT02447003.CLINICAL TRIAL REGISTRATIONClinicalTrials.gov, NCT02447003.
Author Rugo, H S
Awada, A
Curigliano, G
Iwata, H
Toppmeyer, D
Loi, S
Loirat, D
Zhao, J
Adams, S
Schmid, P
Paluch-Shimon, S
Tan, A R
Cortés, J
Campone, M
Karantza, V
O'Shaughnessy, J
Winer, E P
Hui, R
Card, D
Cescon, D W
Nanda, R
Author_xml – sequence: 1
  givenname: S
  surname: Adams
  fullname: Adams, S
  email: Sylvia.Adams@nyumc.org
  organization: Department of Medicine, Perlmutter Cancer Center, New York University School of Medicine, New York, USA. Electronic address: Sylvia.Adams@nyumc.org
– sequence: 2
  givenname: P
  surname: Schmid
  fullname: Schmid, P
  organization: Centre for Experimental Cancer Medicin, Barts Cancer Institute, Queen Mary University London, London, UK
– sequence: 3
  givenname: H S
  surname: Rugo
  fullname: Rugo, H S
  organization: Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco
– sequence: 4
  givenname: E P
  surname: Winer
  fullname: Winer, E P
  organization: Medical Oncology, Dana-Farber Cancer Institute, Boston, USA
– sequence: 5
  givenname: D
  surname: Loirat
  fullname: Loirat, D
  organization: Institut Curie, Paris, France
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  givenname: A
  surname: Awada
  fullname: Awada, A
  organization: Oncology Medicine Departmen, Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium
– sequence: 7
  givenname: D W
  surname: Cescon
  fullname: Cescon, D W
  organization: Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
– sequence: 8
  givenname: H
  surname: Iwata
  fullname: Iwata, H
  organization: Aichi Cancer Center Hospital, Nagoya, Japan
– sequence: 9
  givenname: M
  surname: Campone
  fullname: Campone, M
  organization: Institut de Cancerologie de l'Ouest, Nantes, France
– sequence: 10
  givenname: R
  surname: Nanda
  fullname: Nanda, R
  organization: Department of Medicin, Section of Hematology/Oncology, The University of Chicago, Chicago, USA
– sequence: 11
  givenname: R
  surname: Hui
  fullname: Hui, R
  organization: Westmead Hospital and the University of Sydney, Sydney, Australia
– sequence: 12
  givenname: G
  surname: Curigliano
  fullname: Curigliano, G
  organization: Department of Oncology and Hematology, University of Milano, Milan; IEO, European Institute of Oncology IRCCS, Milano, Milan, Italy
– sequence: 13
  givenname: D
  surname: Toppmeyer
  fullname: Toppmeyer, D
  organization: Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, USA
– sequence: 14
  givenname: J
  surname: O'Shaughnessy
  fullname: O'Shaughnessy, J
  organization: Baylor University Medical Center, Dallas; Texas Oncology, Dallas; US Oncology, Dallas, USA
– sequence: 15
  givenname: S
  surname: Loi
  fullname: Loi, S
  organization: Division of Research and Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia
– sequence: 16
  givenname: S
  surname: Paluch-Shimon
  fullname: Paluch-Shimon, S
  organization: Breast Cancer Service for Young Women, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
– sequence: 17
  givenname: A R
  surname: Tan
  fullname: Tan, A R
  organization: Levine Cancer Institute, Atrium Health, Charlotte
– sequence: 18
  givenname: D
  surname: Card
  fullname: Card, D
  organization: Merck & Co., Inc., Kenilworth, USA
– sequence: 19
  givenname: J
  surname: Zhao
  fullname: Zhao, J
  organization: Merck & Co., Inc., Kenilworth, USA
– sequence: 20
  givenname: V
  surname: Karantza
  fullname: Karantza, V
  organization: Merck & Co., Inc., Kenilworth, USA
– sequence: 21
  givenname: J
  surname: Cortés
  fullname: Cortés, J
  organization: Breast Cancer Program, Vall d'Hebron Institute of Oncology, Barcelona; Ramon y Cajal University Hospital, Madrid; IOB Institute of Oncology, Quiron Group, Barcelona, Spain
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30475950$$D View this record in MEDLINE/PubMed
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Issue 3
Keywords pembrolizumab
triple-negative breast neoplasms
anti-PD-1
immunotherapy
Language English
License The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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PublicationTitle Annals of oncology
PublicationTitleAlternate Ann Oncol
PublicationYear 2019
References 30753266 - Ann Oncol. 2019 Mar 1;30(3):347-348. doi: 10.1093/annonc/mdz040
References_xml – reference: 30753266 - Ann Oncol. 2019 Mar 1;30(3):347-348. doi: 10.1093/annonc/mdz040
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Snippet Treatment options for previously treated metastatic triple-negative breast cancer (mTNBC) are limited. In cohort A of the phase II KEYNOTE-086 study, we...
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SubjectTerms Adult
Aged
Aged, 80 and over
Anthracyclines - administration & dosage
Antibodies, Monoclonal, Humanized - administration & dosage
Antibodies, Monoclonal, Humanized - adverse effects
B7-H1 Antigen - genetics
Bridged-Ring Compounds - administration & dosage
Cohort Studies
Female
Gene Expression Regulation, Neoplastic - drug effects
Humans
Middle Aged
Neoplasm Metastasis
Progression-Free Survival
Taxoids - administration & dosage
Triple Negative Breast Neoplasms - drug therapy
Triple Negative Breast Neoplasms - genetics
Triple Negative Breast Neoplasms - pathology
Title Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study
URI https://www.ncbi.nlm.nih.gov/pubmed/30475950
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