Prognostic and predictive value of epidermal growth factor receptor tyrosine kinase domain mutation status and gene copy number for adjuvant chemotherapy in non-small cell lung cancer.
OBJECTIVE
Patients with non-small cell lung carcinoma with epidermal growth factor receptor (EGFR) mutations may have a more favorable prognosis and greater response to chemotherapy. The effect of EGFR mutation and gene copy on patients with early-stage non-small cell lung carcinoma receiving adjuvant chemotherapy has not been reported.


METHODS
Tumor samples from NCIC Clinical Trials Group JBR.10, an adjuvant trial of vinorelbine/cisplatin adjuvant chemotherapy [ACT] versus observation (OBS), were analyzed for EGFR mutation by multiple sensitive methods and copy number by fluorescent in situ hybridization. Their prognostic and predictive roles were explored in correlation with survival.


RESULTS
Mutation results were available in 221 OBS and 215 ACT and fluorescent in situ hybridization results in 159 OBS and 163 ACT patients. Mutations were identified in 43 (27 OBS and 16 ACT) patients (36 sensitizing exon 19 deletions or L858R mutations). Compared with wild-type, sensitizing mutations were not significantly prognostic in OBS patients (hazard ratio [HR]: 0.79, 95% confidence interval [CI]: 0.38-1.63, p = 0.53). Although the presence of sensitizing mutations resulted in relatively greater benefit in ACT patients (HR: 0.44, 95% CI: 0.11-1.70, p = 0.22) compared with wild-type patients (HR: 0.78, 95% CI: 0.58-1.06, p = 0.12), this quantitative difference was not significant (interaction p = 0.50). Similarly, high EGFR copy was neither significantly prognostic nor predictive, although quantitatively it was associated with greater benefit from ACT.


CONCLUSIONS
Trends toward longer survival and a greater benefit from chemotherapy were observed in patients with exon 19/21 mutations and high EGFR copy, although the differences were not statistically significant. The interpretation of the results was limited by the low EGFR mutation rate in this study of mainly white patients.
Department of Pathology, University Health Network, Princess Margaret Site, Ontario, Canada.
Ming-Sound
MS
Tsao
Akira
A
Sakurada
Keyue
K
Ding
Sarit
S
Aviel-Ronen
Olga
O
Ludkovski
Ni
N
Liu
Aurélie
A
Le Maître
David
D
Gandara
David H
DH
Johnson
James R
JR
Rigas
Lesley
L
Seymour
Frances A
FA
Shepherd
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D015996:Survival Rate; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
D004273:DNA, Neoplasm; D014747:Vinblastine; C512478:EGFR protein, human; D066246:ErbB Receptors; D002945:Cisplatin; D000077235:Vinorelbine