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FAQs: Optimizing Management of Patients with Triple-Negative Breast Cancer

Mark Pegram, MD

Medical Oncology
Stanford University
Palo Alto, California

Mark Pegram, MD: consultant/advisor/speaker: AstraZeneca/Daiichi Sankyo, Gilead, Roche/Genentech.

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Sara Tolaney, MD, MPH

Associate Professor of Medicine
Division of Breast Oncology
Harvard Medical School
Chief, Division of Breast Oncology
Breast Oncology Program
Dana-Farber Cancer Institute
Boston, Massachusetts

Sara Tolaney, MD, MPH: consultant/advisor: 4D Pharma, AstraZeneca, ARC Therapeutics, Athenex, BeyondSpring, Blueprint Medicines, Bristol-Myers Squibb, Certara, Chugai Pharmaceuticals, CytomX, Daiichi Sankyo, Eisai, Ellipses Pharma, Genentech/Roche, Gilead, Infinity Therapeutics, Lilly, Menarini/Stemline, Merck, Mersana Therapeutics, Myovant, Novartis, Odonate, OncoSec Medical Incorporated, Pfizer, Reveal Genomics, Sanofi, Seattle Genetics, Umoja Biopharma, Zentalis, Zymeworks; steering committee: CytomX, Lilly, OncXerna; researcher (paid to institution): AstraZeneca, Bristol-Myers Squibb, Cyclacel, Eisai, Exelixis, Genentech/Roche, Gilead, Lilly, Merck, NanoString Technologies, Nektar, Novartis, Odonate, Pfizer, Sanofi, Seattle Genetics.

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Released: January 31, 2023

Key Takeaways

  • The optimal timing of radiation therapy and adjuvant pembrolizumab, whether concurrent or sequential, for early-stage triple-negative breast cancer (TNBC) is uncertain and remains at the physician's discretion.
  • Antibody-drug conjugates are associated with chemotherapy‑like side effects due to their cytotoxic payload.
  • Treatment decisions for patients with advanced TNBC require engagement with the pathology laboratory to accurately determine the status of key biomarkers such as BRCA1/2, HER2, and PD-L1.

In this commentary adapted from a discussion between Sara Tolaney, MD, MPH, and Mark Pegram, MD, during a live Cancer Conversations webinar titled, Smarter. Stronger. Together: Optimizing Personalized Triple-Negative Breast Cancer Care for Providers and Patients, held on November 22, 2022, the experts address important clinical questions about how to optimize the management of patients with triple-negative breast cancer (TNBC).

Do patients who are receiving adjuvant pembrolizumab and radiation therapy for triple-negative breast cancer (TNBC) experience lung toxicities?

Mark Pegram, MD:
Most of the available data on lung toxicities from pembrolizumab and radiation are from lung cancer studies. For example, in a recent published pooled analysis of pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer, in a population where most radiotherapy was given for primary lung cancer, lung metastases or intrathoracic nodal metastases, no new safety concerns were noted. Insofar as I am aware, adjuvant pembrolizumab with radiation is not contraindicated.

Sara Tolaney, MD, MPH:
A question that comes up very frequently in the clinic is about how to time radiation when a patient is receiving adjuvant pembrolizumab. In the adjuvant phase of the phase III KEYNOTE-522 trial of pembrolizumab and chemotherapy for patients with newly diagnosed, early-stage TNBC, it was at the physician’s discretion to determine whether or not to administer pembrolizumab concurrently or sequentially with radiation. Hence, as yet, it is not clear if the approach should be to use concurrent or sequential treatment. My understanding, however, is that from an efficacy standpoint, it is reasonable to overlap radiation therapy with immune checkpoint inhibitor therapy. There are lots of data to suggest, at least preclinically, that concurrent therapy may be synergistic, and so, my personal preference has been to try to overlap pembrolizumab and radiation therapy in the adjuvant setting. We need to wait to see the subgroup analysis of the KEYNOTE-522 data regarding the benefits and risks of sequential versus concurrent pembrolizumab and radiation therapy.

What are the biggest challenges you face when administering antibody-drug conjugates (ADCs) in your clinical practice?

Mark Pegram, MD:
The biggest challenge is explaining to patients the expected toxicities associated with the use of ADCs such as sacituzumab govitecan and trastuzumab deruxtecan and explaining that ADCs comprise a cytotoxic payload made from a chemotherapeutic moiety. ADCs as a drug class are just a clever and more potent way to deliver cytotoxic chemotherapy that is tumor directed. As a consequence, there are indeed some chemotherapy‑like side effects that may result from the use of ADCs.  It is important not to underestimate the potential side effects of ADCs when having discussions with patients. It is also important to make sure that patients get what they need in terms of prophylaxis for potential gastrointestinal toxicities and follow the prescribing information with regard to dose modification for side effects such as nausea, elevated liver function tests, fatigue, cytopenias, drug-related pneumonitis, and the like. The prescribing information contained in the package inserts are very detailed and proscriptive in this regard, for all of the available ADCs approved for use in breast cancer by the FDA. 

Sara Tolaney, MD, MPH:
I agree that it is important to discuss the composition of ADCs with patients, because they are sometimes perceived to be solely targeted agents, whereas in fact, they consist of a cytotoxic payload, a monoclonal antibody, and a chemical linker. For this reason, it is critical to use ADCs while keeping the components and the potential adverse events in mind.

How do you approach shared decision-making with your patients with TNBC?

Sara Tolaney, MD, MPH:
The nature of making treatment decisions for our patients can be complex, and so, it is important to ensure shared decision-making with patients. Also, the use of a multidisciplinary treatment decision approach is important. For instance, it is important to engage the pathology laboratory to determine the status of biomarkers such as HER2, and PD-L1, and BRCA1/2, and to review images with our radiology colleagues. We also need to involve our palliative care physicians as needed. 

Mark Pegram, MD:
The use of a tumor board is important, and it helps to make important multidisciplinary treatment plans. A tumor board is the ideal venue for going over complex treatment decision-making between multiple medical disciplines or specialties. Another critical approach is to spend more time with individual patients (and their caregivers), as making treatment decisions has become quite complicated due to the availability of newly approved agents in breast cancer. This is of course a good thing, because we now have, for many clinical circumstances, multiple good options to choose from. It is important to discuss the risk‑benefit ratios, the clinical trial opportunities, the costs of treatments, the expected toxicities, and management approaches with patients. It is also essential to involve the caregivers and immediate family members in the treatment decision making process.

Sara Tolaney, MD, MPH:
I totally agree. It can be very complicated to explain all these factors and potential toxicities to patients. 

Your Thoughts?
What are the challenges you face when treating your patients with advanced TNBC? Please answer the polling question and join the conversation by posting a comment in the discussion section.

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Supported by an educational grant from
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