What second-line therapy would you offer a patient with metastatic colon cancer with HER2 IHC 3+ amplification and KRAS G12D mutation whose disease progressed on FOLFOX?  

This is a rare but interesting situation since HER2 IHC 3+ is only found in <3% metastatic colorectal cancer (mCRC) while KRAS G12D mutation is about 12% in the mCRC population. This combination is quite uncommon. The best evidence would be from the DESTINY-CRC02 (Raghav et al., PMID 39116902), w...

It is important to remember the clinical context of the modern HER2 trials:1. MOUNTAINEER (Strickler et al., PMID 37142372): Chemotherapy Refractory ("fluoropyrimidines, oxaliplatin, irinotecan, an anti-VEGF monoclonal antibody, and an anti-PD-L1 or anti-PD-1 monoclonal antibody if the tumour had mi...

Thanks for the important question!I think the patient has choices. Could consider FOLFIRI second line. Notably trastuzumab-based combinations (tucatinib, lapatinib, and pertuzumab) do not result in significant benefit when concurrent KRAS mutation is noted (which can occur pretty much like your pati...