Neratinib is an irreversible pan-HER inhibitor approved for patients with HER2 amplified breast cancer. MutHER trial evaluated the antitumor activity of neratinib and neratinib in combination with fulvestrant for HER2 non-amplified metastatic breast cancer harboring activating mutations in HER2, a population otherwise not eligible for HER2-targeted therapy. The study demonstrated the antitumor effect of neratinib, especially in invasive lobular breast cancer. Interestingly, responses were observed with the addition of trastuzumab to neratinib upon disease progression, suggesting dual HER2 blockade may be important in targeting HER2 mutation. Further investigation of trastuzumab in combination with neratinib is therefore warranted.

Fusions involving the NTRK1/2/3 genes have been identified in many tumor types, several of which often metastasize to the CNS. Entrectinib is a potent TRK inhibitor that was specifically designed to penetrate and remain in the CNS. Demetri and colleagues present the latest results of an integrated analysis of three phase I/II trials:...

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