Real-World Access, Implementation Challenges, and Unanswered Questions in HER2-Targeted Therapy

This segment shifts focus from clinical trial data to the practical realities of delivering HER2-targeted therapies in community and real-world settings. Dr. Ruta Rao opens by highlighting logistical challenges including infusion capacity, prior authorizations, ADC availability, and disparities in CNS-directed treatment access.

Dr. Gradishar emphasizes that although large academic centers may have the infrastructure to navigate these barriers, smaller practices face significant resource constraints. Infusion-based therapies can bottleneck clinic capacity, and administrative hurdles like payer denials or delayed imaging complicate treatment schedules.

Dr. Gadi expands on these challenges, noting that supportive care extends beyond the drug itself. Coordinating antiemetics, referrals to pulmonology or cardio-oncology, and timely imaging, which are all essential for optimal patient management, can be disrupted by patient and system-level factors. He characterizes this as a “death by a thousand cuts” scenario, where small inefficiencies cumulatively impact care.

Dr. Mouabbi underscores disparities in community and rural settings, where oral therapies are often favored due to travel and logistical barriers, limiting patient access to newer infusion-based ADCs. He points to emerging solutions, such as subcutaneous formulations of T-DXd, which may allow administration closer to home.

The panel then transitions to data gaps and future trial priorities. Dr. Gadi calls for post-marketing and real-world studies to evaluate sequencing strategies, particularly ADC-after-ADC use, and to ensure trial populations reflect diverse patient demographics, including Black Americans. Dr. Mouabbi highlights the potential of cellular therapies (CAR-T and NK cell approaches) targeting HER2 as a promising option for heavily pretreated patients.

Finally, Dr. Gradishar raises the global perspective, emphasizing that affordability and access remain critical issues, not only in the U.S. but worldwide, where breast cancer incidence is rising. Collectively, the discussion underscores the need for research, infrastructure, and innovation to translate scientific advances into equitable real-world outcomes.