How do you prioritize treatment in a lung cancer patient who has HER2 IHC3+ along with other actionable mutations that have tumor-specific drugs available?

Non-small cell lung cancer (NSCLC) can harbor different HER2 alterations: HER2 protein overexpression (2-35%), HER2 gene amplification (2-20%), and HER2 gene mutations (1-4%). Unlike breast or gastric cancer, HER2 protein overexpression in NSCLC is not a validated biomarker for first-line HER2-targe...

For all cancers, it is important to balance the expected antitumor activity of agents with tumor-specific approvals as well as adverse event profiles to personalize treatment choice and sequence of therapies.

Non-small cell lung cancer (NSCLC) can harbor different HER2 alterations: HER2 protein overexpression (2-35%), HER2 gene amplification (2-20%), and HER2 gene mutations (1-4%). Unlike breast or gastric cancer, HER2 protein overexpression in NSCLC is not a validated biomarker for first-line HER2-targe...

I would target the actionable mutation first. Close monitoring is advised given that HER2 overexpression is a resistance mechanism to targeted treatments and may result in a lower response rate or shorter PFS when present upfront. Cases like this may ultimately benefit from dual targeting (simultane...