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News
With two new HER2-directed TKIs and an antibody-drug conjugate now approved for HER2-mutated NSCLC, oncologists are shifting focus from whether to target HER2 to how to sequence treatments. Experts at an OncLive workshop largely favored zongertinib upfront, citing better tolerability and intracranial activity. Brain metastasis control and adverse effect management remain the biggest unmet needs.
The treatment landscape for HER2-mutated non–small cell lung cancer (NSCLC) has rapidly evolved, with two FDA-approved HER2-directed TKIs — zongertinib (approved February 2026) and sevabertinib (approved September 2026) — plus the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) now available. At a recent OncLive Scientific Interchange and Workshop, a panel of oncology experts tackled the real-world question: how do you sequence these agents for the best outcomes?
For treatment-naive patients, the panel unanimously favored zongertinib, pointing to its strong response rates and more manageable side effect profile compared to sevabertinib, which carries a notable daily diarrhea burden. When patients progress on zongertinib, the brain is often the first site of relapse — making intracranial control a top priority. Experts recommended early radiation oncology referral and reserving stereotactic radiosurgery for residual disease. T-DXd was flagged with caution in patients with pre-existing anemia or pneumonitis due to ILD risk.
Key Takeaways:
Why it matters: As HER2-mutated NSCLC treatment options multiply, clinicians need clear frameworks for sequencing. Brain metastasis control and daily tolerability are now the defining factors — and getting the order right could meaningfully impact both survival and quality of life.
