Incomplete Upfront Biomarker Testing in Community Practice: Consequences and Barriers

Dr. Doroshow addresses the critical gap that shaped Sandra's treatment trajectory: incomplete upfront molecular testing in community oncology. Sandra received only limited biomarker testing due to her community oncologist's insurance coverage concerns for comprehensive next-generation sequencing. Her HER2 Y772_A775dup mutation was not identified until disease progression, 12 months into chemo-immunotherapy.Dr. Doroshow explains this problem is unfortunately common, extending beyond limited panels. Some patients receive no molecular testing at all, while others get only liquid-based biopsies that can miss important alterations. She highlights cases where comprehensive testing is performed but results are never acted upon. If Sandra's HER2 mutation had been identified upfront, the team likely would have excluded pembrolizumab from first-line treatment, given limited evidence that immunotherapy benefits patients with HER2-mutant non-small cell lung cancer.

The discussion explores why comprehensive next-generation sequencing is now recommended for all patients with advanced solid tumors, while acknowledging real-world barriers community clinicians face. These include heavy patient loads making it difficult to keep up with rapidly evolving guidelines across tumor types, cost and coverage concerns despite Centers for Medicare and Medicaid Services directives supporting coverage, and significant variability among vendors in billing practices and patient financial responsibility. Dr. Doroshow adds that specialists develop vendor relationships and understand which companies pursue patient collections versus those absorbing costs for uninsured patients—institutional knowledge community practices may lack.

In the next episode, "Managing Brain Metastases in HER2-Mutant NSCLC: CNS Activity and Integration with Local Therapy," Dr. Doroshow discusses how brain metastases influence HER2-directed therapy selection and the integration of stereotactic radiosurgery with systemic treatment.