Case-Based Frontline Decisions in HER2-Mutant NSCLC

This episode applies the discussion to two patients with HER2-mutant non–small cell lung cancer. The first is a former smoker with symptomatic metastatic nonsquamous disease, liver metastases, low-level PD-L1 expression, and an ERBB2 exon 20 insertion identified on tissue sequencing. The panel favors frontline oral targeted therapy for this working primary earner and describes how a community oncologist new to HER2 can choose among zongertinib, sevabertinib, and trastuzumab deruxtecan using trial data, safety, NCCN guidelines, and decision support tools. The second is a woman who has never smoked, with small, asymptomatic brain metastases and no edema, already referred for stereotactic radiosurgery. The faculty describe deferring radiation, citing the central nervous system activity of the targeted agent, and recommend sharing the intracranial data with radiation oncology and reassessing with an early interval MRI before committing to local therapy.