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Professor of Medicine
Director, Breast Oncology and Clinical Trials Education
Division of Hematology/Oncology
Department of Medicine
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California
Hope S. Rugo, MD, has disclosed that she has received funds for research support from Daiichi Sankyo, Eisai, Genentech, Immunomedics, Lilly, Macrogenics, Merck, Novartis, OBI, Odonate, Pfizer, Seattle Genetics, and Sermonix; consulting fees from Puma and Samsung; and funds for non-CME services from AstraZeneca, Daiichi Sankyo, Macrogenics, Merck, Mylan, Novartis, and Pfizer.
As the COVID-19 pandemic continues to impact daily practice, how can we ensure continuity and safety in the care of our patients with advanced breast cancer? In this commentary, I will review recommendations from the COVID‑19 Pandemic Breast Cancer Consortium and provide insights from my own practice.
COVID‑19 Pandemic Breast Cancer Consortium Recommendations
The COVID‑19 Pandemic Breast Cancer Consortium is a group of breast cancer experts from cancer centers across the United States who issued recommendations on treatment strategies for patients with breast cancer back in April 2020, during the initial phase of the COVID-19 pandemic. These recommendations have been used to prioritize which patients should initiate or defer treatment, and how to structure treatments to mitigate risks to patients and providers.
For patients with advanced‑stage invasive breast cancer, the Consortium’s recommendations include adjusting the dose and schedule of systemic therapy. Specifically, for patients with HER2‑positive breast cancer, we can increase the dosing intervals for trastuzumab, pertuzumab, and antibody–drug conjugates. However, in my opinion, this depends on how long patients have been receiving treatment and how well you think they are doing. For example, you could consider interruption of trastuzumab‑based maintenance in patients with more than 2 years of disease control and limited disease burden.
For those with hormone receptor‑positive breast cancer, we should consider the potential toxicity risks of oral targeted therapy. Interestingly, the data we have to date suggest no increased risk for severe COVID-19 outcomes in patients receiving targeted therapies (primarily CDK4/6 inhibitors, for which the bulk of the data are available). I think that is reassuring and very important. The Consortium recommends that delaying first- or second-line CDK4/6 inhibitors can be reasonable in patients likely to maintain tumor control with endocrine therapy alone. However, I would argue that we have seen survival benefits in the first‑line setting in pre- and perimenopausal women and in the second‑line metastatic setting in patients on fulvestrant. For that reason, in my practice, I did not delay the use of CDK4/6 inhibitors. And again, to date, we have not seen an increase in COVID-19 infection frequency or worsening outcome. I think that is very encouraging.
For mTOR inhibitors and PI3 kinase inhibitors, it depends on how the patient is tolerating therapy. For example, you do not want a patient to develop ketoacidosis from hyperglycemia. Dose reductions can reduce toxicity and neutropenia, and reduce the number of in-office visits (for blood draws, etc). These are important considerations for reducing exposure for both our patients and our staff.
Case Study: Managing a Patient With Metastatic Breast Cancer
Let’s consider an example case of a 63-year-old woman with HR+ metastatic breast cancer for whom therapy is likely to improve outcomes, including longer disease control and potentially better survival. How should she be managed in the context of the ongoing COVID-19 pandemic?
I would move forward with treatment. That is how we have managed patients like her at my cancer center; we have treated those presenting with metastatic disease who are symptomatic. My choice would be endocrine therapy, if possible, in patients without pending visceral crisis or immediately life‑threatening disease. That allows patients to come in once a month for evaluation of their metastatic disease. They would also need blood tests performed locally, and honestly, I am not certain if sending patients into a large reference laboratory is any safer than coming into our cancer center, where we have instituted very careful policies. I think that is an individual decision.
Immune Checkpoint Inhibitors and COVID‑19
Use of immune checkpoint inhibitors in patients who may have COVID-19 has been a big issue. It has been thought that checkpoint inhibitors might both increase the risk of contracting COVID‑19 and increase the risk of having a bad outcome. Some patients deferred their checkpoint inhibitor therapy for a while because of these concerns. However, it is not clear to me that there is an association. I suspect that we may be seeing an overlap between the comorbidities that increase the risk of COVID‑19 infection and complications and the patient populations for whom we would most likely choose immunotherapy.
In my practice, a lot of patients are receiving immunotherapy, either as part of clinical trials or, based on regulatory approval, for PD-L1–positive metastatic triple‑negative breast cancer. Based on my experience, I think we can safely administer immunotherapy if using proper precautions in an adequately resourced setting. It has been suggested to consider screening for COVID-19 prior to initiating immunotherapy, but we do not screen beyond symptom screening at each visit.
For patients with a current COVID‑19 infection, we need to delay immunotherapy, as well as any other treatments that can be feasibly delayed. I would avoid any drug that can cause pneumonitis or suppresses the immune system. For example, I would delay CDK4/6 inhibitors in a patient with an active COVID‑19 infection. Similarly, I would not administer chemotherapy or tamoxifen, because we have seen that hypercoagulability goes hand in hand with COVID‑19. Agents I would feel comfortable continuing in this setting include trastuzumab, pertuzumab, and aromatase inhibitors.
Which strategies have you implemented to ensure continuous care and COVID-19 risk mitigation for your patients with advanced breast cancer? Answer the polling question and join the discussion by posting a comment below.