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Professor of Medicine
Harvard Medical School
Dana-Farber Cancer Institute
Harold J. Burstein, MD, PhD, has no relevant conflicts of interest to report.
One of the new challenges for breast cancer care during the COVID-19 pandemic has been managing patients with cancer who have respiratory symptoms or fever. Distinguishing possible COVID-19 cases from patients whose symptoms are related to their cancer or to their cancer treatment has introduced an operational complexity that our staff and our nurses are working through. We have become more adept at managing this challenge over time, as testing for SAR-CoV-2 has become more widespread, but we have had to put systems in place for referring patients for testing and for how they will be managed until we have the test result.
Consider the case of a 47-year-old woman who is receiving trastuzumab deruxtecan for metastatic HER2-positive breast cancer and calls her oncologist to report wheezing and breathlessness. What is the optimal response, recognizing that her symptoms could easily be a treatment-related pneumonitis, or shortness of breath related to a trastuzumab-type cardiomyopathy, or could be the onset of COVID-19, or could be plain old non–COVID-19 pneumonia or an upper respiratory infection?
There is no specific “best approach” in such cases, but they do require more thought than we might have needed previously. We would want to assess the patient, obtain a SARS-CoV-2 test, if possible, and a CT scan to look for changes linked to COVID-19–associated pneumonitis, although those are nonspecific. The patient may have treatment-related toxicities from trastuzumab deruxtecan, and all of these possibilities should be considered as part of your differential diagnosis. At my center in Boston, we require SARS-CoV-2 testing for patients who are symptomatic before they come in for a CT scan, for instance—unless they are acutely sick, in which case they go straight to the emergency department.
Managing Trastuzumab Deruxtecan–Induced Interstitial Lung Disease (ILD)
There is a risk of pneumonitis, or ILD, with trastuzumab deruxtecan, which requires specific management. In the phase II DESTINY-Breast01 study, trastuzumab deruxtecan demonstrated durable efficacy in pretreated patients with HER2-positive unresectable or metastatic breast cancer. ILD was identified as the key risk associated with use of trastuzumab deruxtecan in this study, occurring in 25 (13.6%) patients, of whom 4 (2.2%) died. Patients receiving trastuzumab deruxtecan should be monitored closely for symptoms such as cough, fever, shortness of breath, or any other new or worsening respiratory symptoms.Those individuals who develop grade ≥ 2 ILD or pneumonitis must permanently discontinue trastuzumab deruxtecan. Steroids should be initiated promptly in cases where ILD or pneumonitis are suspected.
Immune Checkpoint Inhibitors (ICIs) and COVID-19
One of the other big questions concerning oncologists during the COVID-19 pandemic has been the use of ICIs. We are using these drugs in patients with triple-negative breast cancer who have tumors that are PD-L1 positive, typically in combination with chemotherapy. There are data linking ICI use with severe illness and hospitalization in patients with cancer and COVID-19, though very few reports on outcomes in breast cancer, and it is not clear how these data apply to breast cancer patients. It may be that ICIs are overstimulating the immune system, or understimulating it, both of which could be a problem in patients with COVID-19; we do not have much data at this point. The key question to ask is whether your patient really needs the ICI or chemotherapy. If the patient is in a maintenance phase or if there is ambiguity over PD-L1 expression, this may be a good time to speak with the patient about whether it is worth taking this class of drugs now, as opposed to later.
Aside from trastuzumab deruxtecan and ICIs, we may also see ILD/pneumonitis with CDK4/6 inhibitors, as well as with chemotherapy—I saw a patient for consultation recently who had developed pneumonitis from paclitaxel. Patients receiving these therapies should be counseled on the importance of contacting their healthcare providers in case of a dry cough with or without fever and should be monitored regularly for pulmonary symptoms or radiologic changes indicative of ILD or pneumonitis (such as hypoxia, cough, dyspnea, and interstitial infiltrates). Now we have also added COVID-19 to the possible causes of these symptoms in an oncology clinic.
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What questions do you have about caring for your patients with breast cancer during this ongoing pandemic? Register here to attend CCO’s upcoming online Webinars, “COVID-19: Ensuring the Quality, Resiliency, and Continuity of Breast Cancer Care During a Pandemic,” presented by Hope S. Rugo, MD, during which Dr. Rugo will answer your questions.