This episode makes the case for moving HER2-targeted therapy into the first-line setting. The panel describes how a frontline approval allows clinicians to spare patients with HER2-mutant non–small cell lung cancer the toxicity of platinum-based chemotherapy, and why patients with EGFR, ALK, and ERBB2 alterations may derive limited benefit from immunotherapy. Faculty emphasize using the most effective therapy up front, noting that a substantial share of patients never receive second-line treatment, and place trastuzumab deruxtecan and sevabertinib later in the sequence. The discussion then turns to the Beamion LUNG-1 data for zongertinib, with response rates in treatment-naive patients far exceeding historical chemotherapy benchmarks and durability that compares favorably with standard approaches. The panel addresses approval on single-arm data, citing precedent with other tyrosine kinase inhibitors, explaining why response rate captures only meaningful tumor shrinkage and excludes stable disease, and noting an ongoing randomized trial comparing zongertinib with chemoimmunotherapy.
