Managing TNBC

CE / CME

Cases and Challenges in the Optimal Treatment of Triple-Negative BC

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

Nurse Practitioners: 1.00 Nursing contact hours, includes 1.00 hour of pharmacotherapy credit

Released: May 08, 2023

Expiration: May 07, 2024

Jeremy M. Force
Jeremy M. Force, DO

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Immune-Related Adverse Events With ICIs

Treatment with ICIs is generally better tolerated than chemotherapy, but associated with unique immune-related adverse events (irAEs) that are unpredictable and can affect almost any part of the body.20 In practice, irAEs predominantly manifest as gastrointestinal (colitis), dermatologic (rash), endocrine (hypothyroidism), and pulmonary (pneumonitis) toxicities.21 Unfortunately, there is still no reliable way to predict which patients will develop an irAE or how severe of a reaction will occur. There is some evidence to suggest that women are at higher risk for irAE development and severity than men, but whether that is related to biology or some other factor is unknown.22

Many irAEs occur within the first few months of treatment initiation, but some occur later and even after treatment completion. Therefore, it is imperative to maintain a high level of suspicion for irAEs with onset of any changes that patients report during or after treatment. These include nonspecific symptoms such as bloating or weight loss; changes in bowel habits, vision, or mood; cough, dyspnea, or chest pain; rashes or pruritus; and severe fatigue or muscle weakness.21,23,24 Patients should be educated on symptoms and instructed to contact the oncology team if any develop, if they are admitted to hospital, or if they begin any new medications.21,24 It is also helpful to provide patients with a wallet card detailing the type of immunotherapy they are using, potential irAEs, and contact numbers for their oncology team. Instruct patients to carry this with them at all times and to share it with other healthcare providers. A preprinted card is available from the Oncology Nursing Society and endorsed by the American Society of Clinical Oncology (ASCO).21

Thyroid symptoms were common in the clinical trials of pembrolizumab for TNBC: immune-mediated hypothyroidism was the most frequent all-grade irAE, occurring in about 15% in each trial. However, grade 3 or higher hypothyroidism occurred in less than 0.5% of patients. In each trial, the most frequent grade 3 or higher irAE was a severe dermatologic reaction, reported in 4.7% of patients with early breast cancer and 1.8% of patients with metastatic TNBC.15,25

 

Expert Insights From Dr Force: Comparing irAEs in Early-Stage vs Advanced TNBC

 

Recommended Baseline Assessments Prior to ICI Therapy
Recommended baseline assessments and monitoring during and after treatment with ICIs are shown in Table 1 and Table 2.24,26 The most important part of the pretreatment history is determining whether the patient has a history of autoimmune disease. The presence of most autoimmune diseases will contraindicate the use of ICI treatment as the treatment could potentially worsen the effects of the patient’s autoimmune condition.

Table 1. Recommended Baseline Assessments Prior to ICI Therapy24

Table 2. On- and Post-Treatment Monitoring for ICIs24,26

In general, most irAEs are mild to moderate in severity and can be managed with low-dose steroids and, if necessary, treatment interruption. More severe irAEs require treatment interruption and grade 4 irAEs require permanent treatment discontinuation. Given the breadth of potential irAEs, consulting detailed guidelines on their management from the NCCN, ASCO, or the Multinational Association of Supportive Care in Cancer is critical to good care. Prescribing information for the treatment being used can also be helpful in irAE management.21,23,26,27 

Given the prevalence of hypothyroidism, a detailed overview of its management is shown in Table 3. A notable difference from the approach to most irAEs is that steroids are not used, regardless of the severity. Instead, management is based on thyroid replacement therapy.21,23

 

Expert Insights From Dr Force:Strategies for Managing Low-Grade Immune-Related Hypothyroidism

 

Table 3. Guide to Managing Immune-related Primary Hypothyroidism21,23

Which of the following best describes the PD-L1 expression level indicated for the use of first-line pembrolizumab plus chemotherapy in patients with metastatic TNBC?