Comparative Safety Profiles and Risk Management Counseling: ILD Risk and Patient Communication

This episode examines Dr. Doroshow's approach to safety counseling when selecting among HER2-directed therapies, with particular attention to Sandra's concern about interstitial lung disease risk given prior pembrolizumab exposure. Dr. Doroshow addresses what is currently known about interstitial lung disease (ILD) across available HER2-targeted agents and how she frames these discussions with patients. She reviews the current understanding of ILD risk across HER2-directed therapies. Small numbers of cases have been reported to the Food and Drug Administration and in medical literature for both zongertinib and sevabertinib, but incidence appears lower than observed with trastuzumab deruxtecan. With trastuzumab deruxtecan, pneumonitis can be not only clinically significant but potentially disabling or life-threatening, making it a major consideration in treatment selection. She also reviews broader side effect constellation differentiating these agents: cytopenias and significant nausea with trastuzumab deruxtecan; elevated liver function tests, diarrhea, and rash with HER2-selective tyrosine kinase inhibitors; and additional EGFR-related toxicity with sevabertinib.

The discussion centers on Dr. Doroshow's risk management counseling philosophy, which she describes as focusing on one critical message: Patients need to contact the office when they experience symptoms rather than waiting for their next scheduled appointment. Dr. Doroshow explains many patients worry about bothering their physician after hours and assume they should wait until their next visit. She counters this by emphasizing early reporting leads to faster intervention and better outcomes, and patients shouldn’t endure symptoms in silence.

In the next episode, "Financial Access, Patient Assistance Programs, and Adherence Monitoring Strategies," Dr. Doroshow tackles the practical challenges of drug cost and insurance coverage that directly impact Sandra's treatment decisions.