In the case of the HGF treated tumor cell distribution consisting of 90% EGFRL858R and 10% EGFRL858R, T790M, a constant combination of afatinib/trametinib was effective against the EGFRL858R, T790M, HGF+ subpopulation despite overall progression due to the outgrowth of the EGFRL858R, HGF+ tumor cell population, whereas a five day switching regimen between afatinib/trametinib and erlotinib/crizotinib combinations alternately targeted the HGF+ EGFRL858R, T790M and the EGFRL858R subpopulations (Figs 3A and 4B) leading to overall response. Here, HGF is linked to neoplasm.