What action is recommended when LVEF falls to 45–49% with a ≥10% absolute decrease from baseline during pertuzumab/trastuzumab therapy?

• A. Withhold Perjeta and trastuzumab and repeat LVEF in approximately 3 weeks
• B. Continue therapy as planned
• C. Decrease the dose of trastuzumab
• D. Switch to a non-HER2 regimen

Answer: (A)

When a patient on HER2-targeted therapy shows a drop in heart function, the first priority is to protect the heart while still aiming to treat the cancer. If the left ventricular ejection fraction falls to 45–49% with at least a 10-point drop from baseline, this indicates potential reversible cardiotoxicity from the therapy. The best action is to withhold both pertuzumab and trastuzumab and recheck the LVEF in about three weeks. This pause lets the heart recover and prevents progression to symptomatic heart failure, giving clinicians information to decide whether and how to continue treatment. If the LVEF recovers toward baseline, therapy can be resumed with close cardiac monitoring; if it does not improve, alternatives that do not affect HER2 signaling should be considered, often with input from cardio-oncology.

Continuing therapy as planned could worsen cardiac injury. Decreasing the dose isn’t standard practice for these fixed-dose regimens, and switching to a non-HER2 regimen would be considered only if there’s inadequate recovery or persistent dysfunction, not as the immediate response to a reversible decline.