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Managing mCRC

CE / CME

Opportunities and Challenges in Management of Metastatic Colorectal Cancer

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 02, 2023

Expiration: May 01, 2024

Robert Lentz
Robert Lentz, MD
CME/CE Information

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Immune-Related Adverse Events With ICI Therapy

The adverse events associated with ICI treatment differ in type and timing from those of cytotoxic chemotherapy. irAEs can occur at any time during treatment with an ICI, most frequently 1-3 months after starting treatment. However, some can occur much later, even years after treatment completion.23,24 With pembrolizumab and nivolumab, the most common early irAEs affect the skin and colon, usually developing within 4-6 weeks of treatment initiation and rarely after 10 weeks. Endocrinopathies tend to appear between 6-8 weeks but may develop at any time during treatment. Hepatotoxicity tends to appear between 6-12 weeks after starting therapy and rarely after 14 weeks. With combined nivolumab and ipilimumab, irAEs tend to occur earlier and be more severe.25 

Figure 2. Timing and intensity of irAEs.25 

The most frequently encountered irAEs affect the skin, gastrointestinal tract, thyroid, and liver and generally are manageable. In the gastrointestinal tract, immune-related colitis with diarrhea is the most common irAE, with presentation similar to inflammatory bowel disease but with very rapid symptom development.24,26 Between 5% and 10% of patients may develop liver toxicity, and liver function tests should be closely followed during treatment.27-30 Less frequently occurring but potentially serious irAE include pneumonitis, adrenal insufficiency, new-onset hyperglycemia, and cardiovascular toxicity. Some easily missed irAEs include new or worsening joint pain, dry mouth, neuropathy, or nephritis.24,26 

There is no reliable way to predict which patients will be affected by irAEs. Patients should be educated about irAEs and to contact their oncology team at the first sign of changes such as fatigue, sudden weight change, hot or cold flashes, rash, diarrhea, or dyspnea. Early intervention is the key to managing irAE, and NPs and PAs should maintain a high degree of suspicion for an irAE in patients receiving ICI treatment.27,30

 

Expert Insights From Dr.Lentz: Patient education on immune-related adverse events

 

Recommended baseline assessments before beginning ICI therapy and monitoring during and after treatment with ICIs are shown in Table 2 and Table 3.23,24 The most important part of the pretreatment history is determining whether the patient has a history of autoimmune disease because the presence of most autoimmune diseases will contraindicate ICI treatment as such treatment potentially could worsen the effects of the autoimmune condition. However, baseline treated hypothyroidism, for example, does not preclude immunotherapy, as this condition can be managed during treatment with changes to thyroid hormone supplementation. Ultimately the risks and benefits of immune checkpoint inhibitor therapy and underlying autoimmune disease must be considered and discussed with the patient.

Table 2. Recommended Baseline Assessments Before Starting ICI Therapy24

Table 3. Recommended Monitoring During and After ICI Treatment23,24 

Table 4  and Table 5 summarize ASCO-recommended grading and management of 2 of the most common irAEs in patients with CRC: colitis and hypothyroidism. For colitis, the first step is to rule out an infectious cause of symptoms, such as Clostridioides difficile, and then manage diarrhea with agents such as loperamide. As with most irAEs, more severe symptoms may require systemic steroids to reduce inflammation, and grade 4 symptoms require permanent treatment discontinuation.30

Immune-related hypothyroidism is managed differently than other irAEs because steroids are not part of management. This irAE is managed with thyroid hormone replacement (levothyroxine) and very rarely leads to ICI treatment discontinuation. If treatment must be withheld, it can usually be resumed after thyroid hormone replacement and symptom resolution. A history of hypothyroidism is not a contraindication for treatment with an ICI.30

Table 4. Management of Immune-Related Colitis30

Table 5. Management of Immune-Related Primary Hypothyroidism27,30 

Dermatologic irAEs usually present as a mild maculopapular rash or itching, but severe skin toxicity can occur, including Stevens-Johnson syndrome. Mild dermatologic irAEs are managed using moisturizers or topical steroids plus sun avoidance. More severe reactions require withholding treatment and a systemic steroid. For most patients, treatment can be resumed after symptom resolution.24,27,30

Potentially severe pneumonitis can occur, and it is important to maintain a high level of suspicion for pneumonitis in patients with new-onset respiratory symptoms. Suspected pneumonitis requires assessment with chest CT and pulse oximetry. Grade ≥2 pneumonitis is managed with treatment hold and initiation of systemic steroids. Treatment generally can be restarted after resolution for grade 1/2 events.27,30 

The ICIs used to treat MSI-high/dMMR CRC have similar warnings related to irAEs and their potential to occur in most body systems, but prescribing information for the specific treatment being used should always be consulted to ensure accurate information.20-22 

 

Expert Insights From Dr.Lentz: Patient counseling on the potential for serious irAE

 

Which of these is an adverse event of special interest with trastuzumab deruxtecan?

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