EGFR and KRAS mutations as criteria for treatment with tyrosine kinase inhibitors: retro- and prospective observations in non-small-cell lung cancer.
Results of individualized therapy guided by mutational tumor profile of patients with non-small-cell lung cancer are presented. After confirming the importance of epidermal growth factor receptor (EGFR) and KRAS mutations for (non)response on gefitinib in a retrospective series of patients, EGFR mutations were looked for before--and were a condition for--treatment with gefitinib or erlotinib. To increase the chance to find such a mutation, we selected patients on the basis of smoking status, gender and histopathology. Out of 41 patients selected, 13 (32%) were found to harbor an EGFR mutation. In nine of them it concerned deletions in exon 19 and in none of them KRAS mutations were detected. All nine patients with an exon 19 deletion had a favorable and continuing response to tyrosine kinase inhibitors (TKIs), while four other patients with point mutations responded less favorably: stable disease or a response of short duration. These observations confirm the potential role of EGFR and KRAS mutations in predicting (non)response to TKIs. Exon 19 deletions that are associated with the best responses might be used for first-line treatment selection, while KRAS mutations could play a role in excluding patients from treatment with TKIs.
van Zandwijk
N
N
Department of Thoracic Oncology. Electronic address: n.v.zandwijk@nki.nl.
Mathy
A
A
Department of Thoracic Oncology.
Boerrigter
L
L
Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Ruijter
H
H
Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Tielen
I
I
Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
de Jong
D
D
Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Baas
P
P
Department of Thoracic Oncology.
Burgers
S
S
Department of Thoracic Oncology.
Nederlof
P
P
Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D011905:Genes, ras / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use; D012189:Retrospective Studies; D015996:Survival Rate
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib