Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive:

Emerging Immunotherapy Combination Strategies for Breast Cancer: Dual Immune Checkpoint Modulation, Antibody–Drug Conjugates, and Bispecific Antibodies

2021 Year in Review - Breast Cancer - Breast Cancer

Breast cancer has long been thought to be immune-suppressive.1 PD-L1 expression and/or tumor-infiltrating lymphocytes in the tumor microenvironment have been found in a small percentage of breast tumors in multiple investigations over the past 10 to 15 years.1 The PD-1 inhibitor pembrolizumab has been licensed by the US Food and Drug Administration for the first-line treatment of patients with metastatic PD-L1–positive, triple-negative breast cancer (TNBC) in combination with chemotherapy, and the PD-L1 inhibitor atezolizumab has also shown clinical activity.1 With the inclusion of immunotherapy, the median progression-free survival for pembrolizumab or atezolizumab paired with chemotherapy rose by 4.1 months and 2.5 months, respectively.1

Immune checkpoint blockade is now used as a first- or second-line treatment for a variety of malignancies, but it is still difficult to determine which patients would benefit the most. Because of its link to improved response rates to PD-1/PD-L1 blockage in patients with metastatic TNBC, PD-L1 expression is commonly employed as a prognostic biomarker.2 In patients with metastatic TNBC treated with immune checkpoint inhibitor monotherapy or, in some circumstances, a chemotherapeutic combination, higher PD-L1 positivity has been linked to greater overall response rates, progression-free survival, and overall survival. These findings underscore the need for less confusing, more repeatable immune checkpoint inhibitor prediction indicators.2

Despite this progress, there is still more to be studied. The clinical benefit is minimal. Only approximately 40% of TNBC tumors are PD-L1 positive, and immunotherapy is still not licensed for advanced PD-L1–negative TNBC, HER2-positive breast cancer, or estrogen receptor–positive breast cancer.1 In breast cancer, it is conceivable that redundant immune suppression mechanisms are active, or that key immune activation pathways remain mute.1 Studies are investigating how dual immune checkpoint inhibition, bispecific antibodies, and antibody–drug conjugates can be used to target several pathways of immunoregulation in metastatic breast cancer.1


  1. Roussos Torres ET, Emens LA. Emerging combination immunotherapy strategies for breast cancer: dual immune checkpoint modulation, antibody-drug conjugates and bispecific antibodies. Breast Cancer Res Treat. 2021 Oct 30. Epub ahead of print.
  2. Thomas R, Al-Khadairi G, Decock J. Immune checkpoint inhibitors in triple negative breast cancer treatment: promising future prospects. Front Oncol. 2021;10:600753.
Related Items
Enhertu Received Regular FDA Approval for Patients with Unresectable or Metastatic Breast Cancer
JHOP - June 2022 Vol 12, No 3 published on June 16, 2022 in FDA Oncology Update, Breast Cancer
Pembrolizumab plus Chemotherapy for Neoadjuvant and Adjuvant Therapy in Early Triple-Negative Breast Cancer: KEYNOTE-522
Robert J. Ignoffo, PharmD, FASHP, FCSHP, FHOPA
JHOP - April 2022 Vol 12, No 2 published on May 3, 2022 in From the Literature, Breast Cancer, Checkpoint Inhibitors
Lynparza Receives FDA Approval for Adjuvant Treatment of High-Risk Early Breast Cancer with BRCA Mutation
JHOP - April 2022 Vol 12, No 2 published on May 3, 2022 in FDA Oncology Update, Breast Cancer
Evaluating Adverse Events in Patients with Breast Cancer and HIV Infection Receiving Concomitant Antiretroviral Therapy and Chemotherapy with Curative Intent
Donyika Joseph, PharmD, BCOP, Farnaz Foolad, PharmD, BCPS, Neelam K. Patel, PharmD, BCOP, Meghan Karuturi, MD, MSc, Jaime Kaushik, PharmD, BCOP
JHOP - April 2022 Vol 12, No 2 published on May 2, 2022 in Original Article, Adverse Events, Breast Cancer, Infections
Advances in Breast Cancer Treatments: Are We Extending Patients’ Survival?
Meg Barbor, MPH
JHOP - June 2019 Vol 9, No 2 published on April 28, 2022 in HOPA Highlights, Breast Cancer
Development and Implementation of a Pharmacist-Led Virtual Clinic Improve the Management of Patients with Metastatic Breast Cancer Receiving CDK4/6 Inhibitors
JHOP - March 2022 Vol 12 Special Feature published on March 22, 2022 in HOPA Abstracts, Breast Cancer
Time to Treatment Initiation and Outcomes for Patients with Nonmetastatic Breast Cancer Before and During the COVID-19 Pandemic at Community Cancer Centers
JHOP - March 2022 Vol 12 Special Feature published on March 22, 2022 in HOPA Abstracts, Breast Cancer
Spontaneous Tumor Lysis Syndrome in a Patient with Stage IV HER2-Positive Breast Cancer: Case Report
Blake T. Robbins, PharmD, MBA , Alexander M. Kreimer, PharmD, BCPS , Reema A. Patel, MD, Allison R. Butts, PharmD, BCOP
JHOP - February 2022 Vol 12, No 1 published on March 1, 2022 in Case Reports, Tumor Lysis Syndrome, Breast Cancer
Sacituzumab Govitecan Moves to Second-Line Therapy for Metastatic Triple-Negative Breast Cancer: Applying the Lessons from Clinical Trials to Clinical Practice
February 2022 Clinical Trials to Clinical Practice published on February 3, 2022 in Clinical Trials, Breast Cancer
A Subanalysis of the Phase 3 MONARCH 3 Study of Abemaciclib as Initial Therapy for HR-Positive, HER2-Negative Advanced Breast Cancer
2021 Year in Review - Breast Cancer published on January 21, 2022 in Breast Cancer
© Amplity Health. All rights reserved.