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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): J. Fang
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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