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ASCO 2026 | Future directions for HER2-mutant non-small cell lung cancer
Joshua Sabari, MD, New York University Langone Health, New York, NY, comments on the potential of combination strategies in HER2-mutant non-small cell lung cancer (NSCLC), including combinations with chemotherapy and antibody-drug conjugates (ADCs) like trastuzumab deruxtecan. However, clinicians need to closely monitor efficacy in context with toxicity profile and patient-reported outcomes to determine the benefits of these therapies. Additional brain-penetrant tyrosine kinase inhibitors under investigation include NVL-330, CGT4255, and IAM1363. This interview took place during the 2026 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
I think what we’re going to see is likely more combination strategies, combinations potentially with chemotherapy, as well as potential combinations with ADCs like trastuzumab, drugs, such as tucatinib. Those may improve progression-free survival, and we hope overall survival as well. But we really do need to closely watch the, you know, sort of efficacy in context with the toxicity profile...
I think what we’re going to see is likely more combination strategies, combinations potentially with chemotherapy, as well as potential combinations with ADCs like trastuzumab, drugs, such as tucatinib. Those may improve progression-free survival, and we hope overall survival as well. But we really do need to closely watch the, you know, sort of efficacy in context with the toxicity profile. We know that toxicity or adverse events are really critical in this patient population. So looking at patient reported outcomes can give us an early sign if patients are reporting that they’re benefiting from these therapies over and above just the PFS and the overall survival. Now, there are many other HER2 TKIs coming. There is an agent from Nuvalent, NUV-330. There’s an agent from Cogent, CGT-4255, as well as an agent from Iambic, not found, however a CNS penetrant TKI from Iambic is not found but there is one from Daiichi, DS-8201a and one from Zymeworks, zanidatamab and one from Shanghai Junshi, JS-001 and one from Alphamab, KN026. These are all CNS penetrant TKIs. So it’s essential that we look at patient-reported outcomes on these novel agents as well.
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