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MO12 - Prognostic and Predictive Biomarkers III (ID 96)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
MO12.03 - Biomarker analysis of a randomized, controlled, multicenter clinical trial comparing pemetrexed/cisplatin and gmcitabine/cisplatin as first-line treatment for advanced nonsquamous non-small cell lung cancer (ID 3483)
10:30 - 12:00 | Author(s): Y. Liu
The platinum-based doublet regimen was standard of care in advanced non-small cell lung cancer (NSCLC), but the biomarkers to predict the efficacy of first-line chemotherapy is still controversial.
We collected 239 tumor samples (83.0%) from a a randomized, controlled, multicenter clinical trial, which enrolled 288 treatment naïve nonsquamous NSCLC patients who were randomly assigned (1:1) to experimental group to receive cisplatin plus pemetrexed (PC) or the control group to receive gemcitabine plus cisplatin (GC) every 3 weeks for up to 6 cycles. We evaluated the EGFR mutation by Amplification Refractory Mutation System(ARMS) method and EML4-ALK fusion by real-time PCR. Meanwhile, the mRNA expression of excision repair cross complementation 1 (ERCC-1), thymidylate synthase (TS), ribonucleotide reductase M1(RRM-1), and folatereceptor 1(FR-1) was tested by real-time PCR. All of the EGFR mutation, ALK fusion and mRNA expression were analyzed for the correlation with progression free survival, the primary endpoint in the tiral.
The EGFR mutation rate was 46.6%(110/236) in the overall population and the ALK fusion rate was 12.0%(29/233). The median PFS was similar between the EGFR mutated patients and wild-type patients(6.0m vs 5.7m,p=0.85), however, the patients of EGFR wild-type had better PFS in the PC group compared with GC group (5.7m vs 3.5m, p=0.03). There are no significant difference between groups in EGFR mutated patients(5.6m vs 6.1m, p=0.59). The patients with ALK fusion seem to have better PFS compared with fusion negative patients (7.7m vs 5.7m), but the difference is not significant(p=0.48). The mRNA expression level was available in 225 patients(94.1%) and we determined the median expression as the cutoff value. The TS expression is significantly correlated with ERCC-1(r=0.67,p<0.001) and negatively correlated with FR-1 expression(r=-0.21,p=0.002). EGFR mutation correlated with lower TS expression(p=0.034) and ALK fusion correlated with higher FR-1 expression(p=0.017). The differences of PFS between the high and low expression of ERCC-1, TS, RRM-1and FR-1 was not significant, in both PC group and GC group.
The expression level of ERCC-1, TS, RRM-1and FR-1 could not effectively predict the progression free survival of NSCLC patients receiving platinum-based doublet regimen. The pemetrexed plus cisplatin regimen should be the priority choice for EGFR wild type patients compared with gemcitabine plus cisplatin regimen.
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P1.22 - Poster Session 1 - Epidemiology, Etiology (ID 166)
- Event: WCLC 2013
- Type: Poster Session
- Track: Prevention & Epidemiology
- Presentations: 1
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
P1.22-005 - A Prospective, Molecular Epidemiological Study of EGFR Mutations in Asian Patients with Advanced Non-Small-Cell Lung Cancer with Adenocarcinoma Histology (PIONEER study) - China Subset Analysis (ID 2241)
09:30 - 16:30 | Author(s): Y. Liu
PIONEER (A molecular ePIdemiOlogy study in Asian patients with advanced NSCLC of adEno histology to assess EGFR mutation status; NCT01185314) was a multinational prospective epidemiological study planned to investigate EGFR mutation frequency in patients from Asia with newly diagnosed advanced lung adenocarcinoma (ADC) and the influence of demographic and clinical factors on EGFR mutation frequency. Here we report analysis results for the subset of patients from China.
Patients were aged ≥20 years, with treatment naïve stage IIIB/IV lung ADC. The primary objective was assessment of overall EGFR mutation frequency. The secondary endpoints included investigation of the correlation between EGFR mutation status and demographic and clinical factors and attrition rates of EGFR mutation testing. The acquisition, preparation, and processing of tumor material was performed in line with the routine clinical practice of the participating hospital laboratories. Tumor EGFR mutation status was determined in central labs using amplification refractory mutation system (ARMS)-based EGFR mutation detection kit (Scorpion ARMS IVD2, Qiagen, Crawley, UK). 29 mutations were detectable by this method across Exons 18, 19, 20, and 21.
747 patients were registered in 17 investigational sites in China (50.4% of the overall study population). 46.9% of the patients were female, mean age was 58 years (range 17-83), and 56.4% were never-smokers. 72.4% (541/747) of the samples used for mutation testing were primary tumor. Sample locations include lung (73.5%), local lymph nodes (10.3%), distant lymph nodes (6.3%), pleural effusion (2.5%), pleura (2.0%), and others. sample types include image-guided core biopsy (29.7%), bronchoscopic biopsy (24.1%), incisional biopsy(12.7%), cytology and others. The median time interval taken from order to report of mutation test was 16 days with a range from 3 days to 62 days. EGFR mutation status was successfully evaluated in 741 patients: 372 (50.2%) were mutation positive, 369 (49.8%) were mutation negative. Smoking status and pack years had a statistically significant association with presence of EGFR mutation, but even in regular smokers, the mutation frequency was 35.3%. 12 patients provided both histology and cytology samples. Among these 11 had concordant EGFR mutations status and 1 had mutation results that did not match.
Locations and types of the samples used for EGFR mutation testing were various in clinical practice. The overall EGFR mutation frequency in clinically unselected Chinese ADC was 50.2%. Smoking status and pack years had a statistically significant association with presence of EGFR mutation.