Algorithm of Cheng et al for Molecular Testing of a Lung Adenocarcinoma, Starting with KRAS Mutation Testing

 

Patient selection: lung adenocarcinoma

 

About 25% of patients have a KRAS mutation, which is associated with poor response to EGFR tyrosine kinase inhibitors (TKI).

 

About 75% of lung adenocarcinomas show a wild-type EGFR, which does not have an EGFR mutation and so is resistant to EGFR tyrosine kinase inhibitors (TKI).

 

An adenocarcinoma with a mutated EGFR showing a responsive mutation profile has a 91% chance of responding to EGFR TKI. An adenocarcinoma with a mutated EGFR showing a resistant mutation profile has a 9% chance of responding to EGFR TKI. An ad

 

About 3% of lung adenocarcinomas show an EML4-ALK rearrangement. About half of these will respond to ALK-targeted therapy. A patient negative for the EML4-ALK rearrangment will not respond to ALK-targeted therapy.

 

Testing panel may include:

(1) test for the presence of a KRAS mutation

(2) mutation profile for EGFR

(3) FISH test for EML4-ALK rearrangement

 

KRAS Mutation	EGFR Mutation	EML4-ALK Rearrangement	Therapy
present	NA	NA	other
absent	wild type	present	ALK TKI
absent	wild type	absent	other
absent	mutated	NA	EGFR TKI if responsive mutation