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C. Huang
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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
- Moderators:B. Han, M. Edelman
- Coordinates: 10/29/2013, 10:30 - 12:00, Parkside Ballroom B, Level 1
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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): C. Huang
- Abstract
- Presentation
Background
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.Methods
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.Results
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.Conclusion
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.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)
- Event: WCLC 2013
- Type: Poster Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P1.11-021 - First-line erlotinib versus cisplatin/gemcitabine (GP) in patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC): interim analyses from the phase 3, open-label, ENSURE study (ID 1849)
09:30 - 16:30 | Author(s): C. Huang
- Abstract
Background
Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor, has proven efficacy in second-/third-line advanced NSCLC, and provides superior first-line efficacy to chemotherapy for patients whose tumors harbor activating EGFR mutations. The phase 3, randomized, open-label ENSURE study evaluated erlotinib vs GP in patients from China, Malaysia and the Philippines with EGFR mutation-positive NSCLC.Methods
Patients ≥18 years with histologically or cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and an ECOG PS of 0–2 were randomized 1:1 to receive either erlotinib (oral; 150mg qd until progression/unacceptable toxicity) or GP (G 1250mg/m[2] iv d1 & 8 q3w; P 75mg/m[2] iv d1 q3w for up to 4 cycles). Patients were stratified by EGFR mutation type, PS, gender, and country). Primary endpoint is progression-free survival (PFS) by investigator, with Independent Review Committee (IRC) assessment for sensitivity analysis; other endpoints include objective response rate (ORR), overall survival (OS), and safety. A pre-planned interim analysis was conducted after 73% of PFS events (cut-off 20 July 2012). An additional exploratory updated analysis (cut-off of 19 November 2012), included all planned PFS events.Results
In total, 217 patients were randomized: 110 to erlotinib and 107 to GP. Baseline characteristics were similar in both groups. Efficacy data by treatment arm for the interim and updated analyses are presented (Table 1). PFS by investigator in EGFR exon 19 deletion and exon 21 L858R mutation subgroups is also presented (Table 1). Erlotinib was better tolerated than GP, with treatment-related serious adverse events (SAEs) occurring in 2.7% vs 10.6% of patients, respectively. The most common grade ≥3 AEs of any cause were neutropenia (25.0%), leukopenia (14.4%) and anemia (12.5%) in the GP arm, and rash in the erlotinib arm (6.4%). At the updated analysis (19 November 2012), erlotinib remained better tolerated than GP, with treatment-related SAEs occurring in 3.6% vs 11.5% of patients, respectively. Median duration of follow-up was 10.3 months and 11.7 months for the GP and erlotinib arms, respectively, at latest cut-off. OS data are not yet mature.
p-value significance level: alpha=0.05Efficacy Outcome Interim analysis (cut-off 20 July 2012) Updated analysis (cut-off 19 November 2012) E GP E GP Investigator-assessed PFS Events, n 35 66 61 87 Median, months 11.0 5.5 11.0 5.5 HR (95% CI) 0.34 (0.22–0.51) 0.33 (0.23–0.47) log-rank p-value <0.0001 <0.0001 IRC-assessed PFS Events, n 33 47 51 55 Median, months 11.0 5.6 11.1 5.7 HR (95% CI) 0.42 (0.27–0.66) 0.43 (0.29–0.64) log-rank p-value 0.0001 <0.0001 ORR % 62.7 33.6 68.2 39.3 p-value 0.0001 <0.0001 Disease control rate (DCR) % 89.1 76.6 91.8 82.2 p-value 0.015 0.0354 EGFR exon 19 deletion subgroup PFS Median, months 11.1 4.2 11.1 4.3 HR (95% CI) 0.20 (0.11–0.37) 0.20 (0.12–0.33) EGFR exon 21 L858R subgroup PFS Median, months 8.3 7.1 8.3 5.8 HR (95% CI) 0.57 (0.31–1.05) 0.54 (0.32–0.90) Conclusion
These analyses demonstrate that erlotinib provides statistically significant and clinically meaningful improvement in both investigator-assessed and IRC-assessed PFS compared with GP in Asian patients with EGFR mutation-positive NSCLC. Primary efficacy results were also supported by secondary endpoints including ORR and DCR.
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P3.10 - Poster Session 3 - Chemotherapy (ID 210)
- Event: WCLC 2013
- Type: Poster Session
- Track: Medical Oncology
- Presentations: 2
- Moderators:
- Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P3.10-013 - Open-label, randomized multicentre, phase II trial of Oral vinorelbine (NVBo) or intravenous vinorelbine (NVBiv) with cisplatin (CDDP) in patients (pts) with advanced Non Small Cell Lung Cancer (NSCLC): A Chinese experience (CA225 study) (ID 1188)
09:30 - 16:30 | Author(s): C. Huang
- Abstract
Background
Aim of the study: to evaluate efficacy (CR, PR) of the two formulations with CDDP in advanced NSCLC. Secondary objectives were progression-free survival (PFS), overall survival (OS) and safety.Methods
NVBo, 60 mg/m² (Arm A) and NVBiv, 25 mg/m² (Arm B) were delivered on D1, D8, repeated every 3 weeks. Doses were increased at cycle 2 (NVBo 80 mg/m[2], NVBiv 30 mg/m[2]) according to hematological tolerance. CDDP doses were 80 mg/m[2] D1 every 3 weeks in both arms. Pts received a maximum of 4 cycles in absence of progression.Results
Between 1/2008 and 6/2009, 132 pts were randomized at 6 investigational centres (cut-off date for final analysis: August, 31[st] 2012 - Arm A 67 pts, Arm B 65 pts). One patient in Arm A was not treated. Among the 131 pts analyzed by an independent panel review, PR was 25.8% (95% CI [15.8-38.0]) in Arm A and 23.1% (95% CI [13.5-35.2]) in Arm B, and disease control (PR+SD) 72.7% (95% CI [60.4-83.0]) in Arm A and 72.3% (95% CI [59.8-82.8]) in Arm B. PFS (months) was 6.2 [3.8-7.7] for Arm A and 6.2 [4.9-7.8] for Arm B. One Year Survival was 59% and 61.6 in Arm A and Arm B, respectively, Two Years Survival: 39% Arm A, 38.7% Arm B, and 30 months Survival 29.2% Arm A, 26.9% Arm B. Median dose intensity (DI): NVBo 44.7 mg/m²/week, NVBiv 15.6 mg/m²/week. Relative dose intensity (RDI): NVBo 89.3%, NVBiv 81.5%. The CDDP median DI was 24.6 mg/m[2]/week in Arm A and 24.5 mg/m[2]/week in Arm B, with a RDI of 92.1% and 91.6% respectively. Grade 3/4 neutropenia: 29 pts and 43 cycles Arm A, 56 pts and 106 cycles Arm B. Febrile neutropenia : 4 (6.1%) pts Arm A, 6 (9.2%) pts Arm B. Grade 3 anaemia : 6 (9.1%) pts and 10 cycles Arm A, 13 pts (20%) and 18 cycles Arm B, with grade 4 anaemia in 3 (4.6%) pts and 5 cycles only in arm B. The most frequent non hematological disorders were nausea (8 pts Grade 3 - 12.1% Arm A; 6 pts Grade 3 - 9.2% Arm B) and vomiting (10 pts Grade 3 - 15.2%, 1 pt Grade 4 - 1.5% Arm A; 9 pts Grade 3 - 13.8%, 1 pt Grade 4 - 1.5% Arm B). Diarrhea was reported in 15 (22.7%) and 9 (13.8%) pts in Arm A and Arm B, respectively.Conclusion
Both arms testing NVBo and NVBiv with CDDP reported similar efficacy results in term of Response Rate, PFS and OS, coupled with an optimal safety profile. NVBo is a step forward in the treatment of NSCLC since it optimises treatment convenience thanks to its oral formulation while maintaining a high level of efficacy. -
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P3.10-044 - Overall Survival analysis results of TFINE Study (CTONG 0904): Different Dose Docetaxel plus Cisplatin as First-line Chemotherapy and Then Maintenance Therapy with Single Agent Docetaxel for Advanced non-Small Cell Lung Cancer (ID 2524)
09:30 - 16:30 | Author(s): C. Huang
- Abstract
Background
Docetaxel (75mg/m[2]) has been reported as first-line and maintenance treatment for Western population with advanced NSCLC. Different doses of docetaxel (60mg/m[2]) are currently delivered in Asian population. Pharmacogenomics alterations in taxanes disposition in different ethnic groups may explain this difference. TFINE study was to evaluate the efficacy, safety, and tolerability of Docetaxel in the maintenance setting, and to identify the preferable dose of docetaxel in Asian population. TFINE study demonstrated significant superiority in tolerability and similar efficacy for dose of 60mg/m2 of Docetaxel versus that of 75mg/m2 in first-line Chinese advanced NSCLC patients. And maintenance treatment with docetaxel significantly prolonged PFS compared with BSC. Here we report Overall Survival (OS) data from TFINE (ClinicalTrials.gov NCT01038661).Methods
Previously untreated patients, aged between 18 and 75 years, histologically or cytologically confirmed advanced NSCLC with PS of 0-1 were included. Patients were initially randomized (R1, 1:1) to receive cisplatin (75mg/m2) plus docetaxel of 75 mg/m2 or 60mg/m2 for 4 cycles. Patients with disease control after the initial treatment were subsequently randomized (R2, 1:2) to best supportive care (BSC) or maintenance docetaxel of 60mg/m2 for up to 6 cycles. Genomic DNA was prospectively collected from all enrolled patients. The primary endpoint was PFS since R2, and the secondary endpoints included ORR, overall survival (OS), and toxicity. OS was defined as the time lasting from R2 to death of any cause. The subgroup analysis about OS included gender, historical category, smoking, ECOG PS. The maintenance treatments of every patient were recorded.Results
This randomized study was undertaken in 15 centers in China. Between Dec 2009 and Aug 2011, a total of 382 patients were enrolled to R1 and 179 patients (46.8%) were enrolled to R2 (61 vs. 118). The median follow-up time for OS was 23.5 months (range 20.5, 28.1 months) for patients receiving BSC and 24.4 months (range 22.6, 25.3 months) for patients receiving maintenance docetaxel of 60mg/m2 for up to 6 cycles. Median OS of BSC group (13.7months, [95%CI:12.0, 15.7]) was not significantly different from that of docetaxel group(12.3months,[95%CI:11.2,14.1]) (p=0.77). No difference was found in the subgroup analysis. Post-discontinuation therapy was given at the discretion of the investigator. Numerically more patients in BSC group (n=35, 57.4%) received second-line treatments, including docetaxel, EGFR-TKI or pemetrexed, than those in maintenance group (n=56, 45.5%), although the difference is statistically insignificant (p=0.13). The failure observation of PFS gains translating into OS gains is partially related to post-progression therapy. Preliminary pharmacogenomics analysis demonstrated the CYP3A5*3C(6986 AG/GG) genotype associated with poor PFS and ABCB1:2677 GG genotype demonstrated less neutropenia in Chinese NSCLC patient treated with Docetaxel/DDP regiment, which did not correlated with OS.Conclusion
Although there is no significant benefit in terms of OS with Docetaxel maintenance treatment, our finding for better tolerability suggest that Decetaxel maintenance treatment could be of some benefit to patients with advanced non-small cell lung cancer.
