The impact of initial gefitinib or erlotinib versus chemotherapy on central nervous system progression in advanced non-small cell lung cancer with EGFR mutations.
OBJECTIVE
This retrospective study was undertaken to investigate the impact of initial gefitinib or erlotinib (EGFR tyrosine kinase inhibitor, EGFR-TKI) versus chemotherapy on the risk of central nervous system (CNS) progression in advanced non-small cell lung cancer (NSCLC) with EGFR mutations.


METHODS
Patients with stage IV or relapsed NSCLC with a sensitizing EGFR mutation initially treated with gefitinib, erlotinib, or chemotherapy were identified. The cumulative risk of CNS progression was calculated using death as a competing risk.


RESULTS
One hundred and fifty-five patients were eligible (EGFR-TKI: 101, chemotherapy: 54). Twenty-four patients (24%) in the EGFR-TKI group and 12 patients (22%) in the chemotherapy group had brain metastases at the time of diagnosis of advanced NSCLC (P = 1.000); 32 of the 36 received CNS therapy before initiating systemic treatment. Thirty-three patients (33%) in the EGFR-TKI group and 26 patients (48%) in the chemotherapy group developed CNS progression after a median follow-up of 25 months. The 6-, 12-, and 24-month cumulative risk of CNS progression was 1%, 6%, and 21% in the EGFR-TKI group compared with corresponding rates of 7%, 19%, and 32% in the chemotherapy group (P = 0.026). The HR of CNS progression for upfront EGFR-TKI versus chemotherapy was 0.56 [95% confidence interval (CI), 0.34-0.94].


CONCLUSIONS
Our data show lower rates of CNS progression in EGFR-mutant advanced NSCLC patients initially treated with an EGFR-TKI compared with upfront chemotherapy. If validated, our results suggest that gefitinib and erlotinib may have a role in the chemoprevention of CNS metastases from NSCLC.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Stephanie
S
Heon
Beow Y
BY
Yeap
Neal I
NI
Lindeman
Victoria A
VA
Joshi
Mohit
M
Butaney
Gregory J
GJ
Britt
Daniel B
DB
Costa
Michael S
MS
Rabin
David M
DM
Jackman
Bruce E
BE
Johnson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000556:secondary*; D018450:Disease Progression; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D012008:Recurrence; D012307:Risk Factors
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib