What are the potential side effects and necessary monitoring for a patient receiving Trastuzumab (Herceptin) and Pertuzumab (Perjeta)/Trastuzumab deruxtecan (Enhertu)/Entrectinib (Rozlytrek) therapy?

Monitoring and Management of Patients Receiving Trastuzumab-Based Therapies

Patients receiving trastuzumab-based therapies require regular cardiac monitoring with baseline and periodic assessment of left ventricular ejection fraction (LVEF), cardiac biomarkers, and clinical symptoms to detect and manage cardiotoxicity, which is the most significant side effect of these treatments. 1

Cardiac Monitoring Protocol

Baseline Assessment (Before Treatment)

• Complete cardiac history and risk factor assessment
• 12-lead ECG
• Echocardiography to assess LVEF (baseline LVEF should be ≥50%)
• Cardiac biomarkers (troponin I or T and BNP or NT-proBNP) 1

During Treatment

• For adjuvant setting: Serial monitoring of cardiac function at baseline, 3,6, and 9 months during treatment, then at 12 and 18 months after treatment initiation 1
• For metastatic setting: LVEF should be monitored at baseline and then periodically in the absence of symptoms 1
• Cardiac biomarkers with each cycle or every 3 months 1
• Clinical assessment for symptoms of heart failure at each visit

Cardiotoxicity Management

Asymptomatic LVEF Decrease (≥10% from baseline to <50% or LVEF 40-49%)

1. Cardiology consultation (preferably cardio-oncology specialist)
2. Initiate cardioprotective medications:
   • ACE inhibitors or ARBs
   • Beta-blockers
3. Continue cardiac biomarker monitoring
4. Repeat LVEF assessment within 3-6 weeks
5. Consider continuing trastuzumab with close monitoring 1

Symptomatic Heart Failure or LVEF <40%

1. Withhold trastuzumab until stabilization
2. Urgent cardiology consultation
3. Standard heart failure therapy (ACE inhibitors and beta-blockers)
4. Reassess LVEF after treatment
5. Consider rechallenge with trastuzumab after symptoms resolve and LVEF improves to >50% 1

Other Common Side Effects and Management

Infusion-Related Reactions

• Occurs in approximately 40% of patients with first infusion
• Symptoms: fever, chills, nausea, vomiting, pain, headache, dizziness, dyspnea
• Management: slow or interrupt infusion, administer antipyretics/antihistamines 2

Hematologic Toxicity

• Neutropenia (particularly when combined with chemotherapy)
• Monitor complete blood count before each cycle
• Consider growth factor support if severe 2

Gastrointestinal Effects

• Diarrhea (67% with pertuzumab combination)
• Nausea (42%)
• Vomiting (24%)
• Management: antidiarrheal agents, antiemetics, adequate hydration 2

Dermatologic Effects

• Rash (34%)
• Nail disorders (23%)
• Management: topical treatments, antihistamines for pruritus 2

Neurological Effects

• Peripheral neuropathy (32%)
• Headache (21%)
• Management: dose modification of taxanes if combined, neuropathic pain medications 2

Special Considerations

Trastuzumab Deruxtecan (Enhertu)

• Monitor for interstitial lung disease/pneumonitis (not seen with standard trastuzumab)
• Symptoms: cough, dyspnea, fever, or other respiratory symptoms
• Management: interrupt treatment and promptly investigate with imaging 3

Pertuzumab Combination

• Higher incidence of diarrhea (67% vs 46% with trastuzumab alone)
• Higher incidence of rash and mucosal inflammation
• Similar cardiac monitoring protocol applies 2

Pitfalls and Caveats

1. Do not permanently discontinue trastuzumab for mild, asymptomatic LVEF decrease - Evidence suggests that many patients can safely continue therapy with appropriate cardiac management 4

2. Distinguish between anthracycline and trastuzumab cardiotoxicity:

   • Anthracycline: Type I, often irreversible, dose-dependent
   • Trastuzumab: Type II, often reversible, not clearly dose-dependent 1, 5

3. Increased risk factors for cardiotoxicity:

   • Age >60 years
   • Previous anthracycline exposure
   • Pre-existing cardiovascular disease
   • Hypertension
   • Low baseline LVEF (50-55%) 1

4. Recovery from trastuzumab cardiotoxicity:

   • Most patients recover with appropriate heart failure therapy
   • Standard heart failure medications are effective (ACE inhibitors, beta-blockers)
   • Consider early cardio-oncology consultation for optimal management 1

By implementing this structured monitoring and management approach, clinicians can optimize the safety of trastuzumab-based therapies while maintaining their significant oncological benefits.