Pemetrexed versus gefitinib as a second-line treatment in advanced nonsquamous
nonsmall-cell lung cancer patients harboring wild-type EGFR (CTONG0806): a
multicenter randomized trial.
Author(s): Zhou Q(1), Cheng Y(2), Yang JJ(1), Zhao MF(3), Zhang L(4), Zhang XC(1), Chen
ZH(1), Yan HH(1), Song Y(5), Chen JH(6), Feng WN(7), Xu CR(1), Wang Z(1), Chen
HJ(1), Zhong WZ(1), Liu YP(3), Wu YL(8).
Affiliation(s): Author information:
(1)Department of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong
General Hospital and Guangdong Academy of Medical Sciences, Guangzhou.
(2)Department of Pulmonary Oncology, Jilin Provincial Cancer Hospital, Changchun.
(3)Department of Medical Oncology, The First Hospital of China Medical
University, Shenyang. (4)Department of Respiratory Medicine, Perking Union
Medical Hospital, Beijing. (5)Department of Respiratory Medicine, Jinling
Hospital, Nanjing University School of Medicine, Nanjing. (6)Department of
Medical Oncology, Hunan Cancer Hospital, Changsha. (7)Department of Medical
Oncology, The First People's Hospital of Foshan, Foshan, China. (8)Department of
Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong General Hospital
and Guangdong Academy of Medical Sciences, Guangzhou syylwu@live.cn.
Publication date & source: 2014, Ann Oncol. , 25(12):2385-91
BACKGROUND: CTONG0806 assessed the efficacy of pemetrexed versus gefitinib as
second-line treatment in advanced nonsquamous nonsmall-cell lung cancer (NSCLC)
harboring wild-type epidermal growth factor receptor (EGFR).
PATIENTS AND METHODS: Patients with locally advanced or metastatic nonsquamous
NSCLC harboring wild-type EGFR, detected by direct sequencing, and previously
treated with platinum-based chemotherapy were randomized to receive gefitinib
(250 mg/day) orally or pemetrexed (500 mg/m(2)) i.v. on day 1 of a 21-day cycle
until disease progression or unacceptable toxicity. The primary end point was
progression-free survival (PFS). The Independent Review Committee (IRC) evaluated
all pictorial data.
RESULTS: From February 2009 to August 2012, 161 patients were enrolled, and 157
were assessable (81 in the gefitinib arm, 76 in the pemetrexed arm). Baseline
characteristics were balanced between the two arms. The median PFSs were 4.8
versus 1.6 months in the pemetrexed and gefitinib arms, respectively [hazard
ratio (HR) 0.54, 95% confidence interval (CI) 0.40-0.75, P < 0.001] as confirmed
by IRC evaluation (5.6versus 1.7 months, HR 0.53, 95% CI 0.38-0.75, P < 0.001).
The median overall survival (OS) showed a trend of superiority in the pemetrexed
arm (12.4 versus 9.6 months, HR 0.72, 95% CI 0.49-1.04, P = 0.077).
Quality-of-life assessment showed no marked difference between the arms. No
unexpected adverse events were found. Of 108 patients with sufficient DNA
samples, EGFR mutation status was re-tested by Scorpion amplification refractory
mutation system (ARMS); 32 (29.6%) tested positive (19 in the pemetrexed arm, 13
in the gefitinib arm; median PFS: 8.1 versus 7.0 months, HR 0.94, 95% CI
0.43-2.08, P = 0.877).
CONCLUSIONS: CTONG0806 is the first trial to show significant improvement in PFS
and an improved OS trend with pemetrexed compared with gefitinib as second-line
setting treatment of EGFR wild-type advanced nonsquamous NSCLC. ARMS is superior
to direct sequencing in excluding false-negative patients.
CLINICALTRIALSGOV IDENTIFIER: NCT00891579.
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