Gefitinib has shown some degree of efficacy when given to patients with metastatic non small cell lung cancer who have the L858R Mutation. But a second mutation, at T790M, reduces the drugs effectiveness greatly in combination with the L858R mutation. Another well known resistant mutation is G719S. 
To understand this, read more in the post below and follow the link to the page where these cartoon and wire frame protein structure screen shots of the Double Mutant were taken.
PDB RSCB Article
Let's taake a quick look at another resistive mutant, the G719S mutation, which affects the Ligand in a completely different way. The guanine is replaced by a serine, which likely interacts via hydrogen bonding with the Oxygen of the partially exposed morpholinyl group. This presumably destabilizes otherwise more favorable interactions between the Ligand and Target Enzyme.
This mutant has two amino acid side chains that work to destabilize the Ligand in the active site. The L858R mutation likely interacts with the morpholinyl group's oxygen but this interaction is destabilized by potential hydrogen bonding with the T790M methionine residue across the active site.
