Efficacy of epidermal growth factor receptor inhibitors versus chemotherapy as second-line treatment in advanced non-small-cell lung cancer with wild-type EGFR: a meta-analysis of randomized controlled clinical trials.
BACKGROUND
EGFR mutation status is closely related to the efficacy of EGFR-TKIs in advanced non-small cell lung cancer (NSCLC). EGFR-TKIs have become the standard first-line treatment for advanced EGFR-mutation NSCLC, while for EGFR wild-type tumors, the preferred first-line treatment is chemotherapy. However, the efficacy of EGFR-TKIs as second-line treatment in EGFR wild-type NSCLC remains controversial. We sought to evaluate the effectiveness of EGFR-TKI as second-line treatment in EGFR wild-type NSCLC.


METHODS
Randomized controlled trials that compared EGFR-TKIs with chemotherapy in previously treated advanced NSCLC with wild-type EGFR were included. We performed a meta-analysis to evaluate the effectiveness of EGFR-TKIs compared with standard chemotherapy. The endpoints were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).


RESULTS
Six randomized controlled trials with a total of 990 patients with wild-type EGFR were included: 499 in the EGFR-TKIs group and 491 in the chemotherapy group. The results indicated that in the second-line treatment of EGFR wild-type advanced NSCLC, PFS was significantly inferior in the EGFR-TKIs group versus the chemotherapy group (HR=1.37, 95% CI=1.20-1.56, P<0.00001). However, this significant difference did not translate into OS (HR=1.02, 95% CI=0.87-1.20, P=0.81). ORR tended to favor chemotherapy but there was no significant difference compared with EGFR-TKI (RR=1.77, 95% CI=0.90-3.50, P=0.10).


CONCLUSIONS
Chemotherapy improves PFS significantly but not OS, compared with EGFR-TKIs as a second-line treatment in advanced NSCLC with wild-type EGFR. Whether EGFR-TKIs should be used in EGFR wild-type patients should be considered carefully.
Guangdong Cardiovascular Institute, Guangdong General Hospital & Guangdong Academy of Medical Science, Guangzhou, PR China; Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Science, Guangzhou, PR China.
Ning
N
Zhao
Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Science, Guangzhou, PR China.
Xu-Chao
XC
Zhang
Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Science, Guangzhou, PR China.
Hong-Hong
HH
Yan
Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Science, Guangzhou, PR China.
Jin-Ji
JJ
Yang
Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Science, Guangzhou, PR China. Electronic address: syylwu@live.cn.
Yi-Long
YL
Wu
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
Chemotherapy; EGFR wild-type; EGFR-TKI; Erlotinib; Gefitinib; Meta-analysis; Non-small cell lung cancer