High efficacy of first-line gefitinib in non-Asian patients with EGFR-mutated lung adenocarcinoma.
BACKGROUND
Several Asian studies demonstrated feasibility of front-line administration of gefitinib for the treatment of non-small cell lung carcinomas (NSCLCs) harboring intragenic epidermal growth factor receptor (EGFR) mutations. The experience of the use of this EGFR tyrosine kinase inhibitor (TKI) in non-Asian subjects remains limited.


METHODS
The study included lung adenocarcinoma (AC) patients treated at the N.N. Petrov Institute of Oncology (Russia).


RESULTS
DNA analysis of 192 consecutive AC revealed 38 (20%) TKI-sensitizing mutations. Presence of the exon 19 deletion (del19) or L858R was strongly correlated with nonsmoking status (smokers: 8/98 (8%); non-smokers: 30/94 (32%); p = 0.00004). The efficacy of first-line gefitinib therapy was evaluated in 25 patients with EGFR-mutated advanced AC. Twelve (48%) cases demonstrated tumor response (1 (4%) complete response, 11 (44%) partial responses; 10/17 (59%) patients with del19 mutation vs. 2/8 (25%) cases with L858R substitution, p = 0.11). The remaining 13 (52%) patients experienced disease stabilization. Median progression-free survival was 8.0 months. Grade 3 toxicity was the maximal adverse event, being observed only in 4 (16%) cases.


CONCLUSIONS
Gefitinib may be considered as an upfront treatment option for EGFR-mutated NSCLC.
Moiseyenko
Vladimir M
VM
N.N. Petrov Institute of Oncology, St.-Petersburg, Russia.
Procenko
Svetlana A
SA
Levchenko
Evgeny V
EV
Barchuk
Alexey S
AS
Moiseyenko
Fedor V
FV
Iyevleva
Aglaya G
AG
Mitiushkina
Nathalia V
NV
Togo
Alexandr V
AV
Semionov
Igor I
II
Ivantsov
Alexandr O
AO
Matsko
Dmitry E
DE
Imyanitov
Evgeny N
EN
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002872:Chromosome Deletion; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D012426:Russia; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib