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MO06 - NSCLC - Chemotherapy I (ID 108)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:R. Perez-Soler, P.M. Ellis
- Coordinates: 10/28/2013, 16:15 - 17:45, Parkside Ballroom A, Level 1
MO06.13 - BEYOND: a randomized, double-blind, placebo-controlled, multicentre, phase III study of first-line carboplatin/paclitaxel (CP) plus bevacizumab (Bv) or placebo (Pl) in Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) (ID 2756)
16:15 - 17:45 | Author(s): G. Chen
Bevacizumab, a monoclonal antibody that inhibits angiogenesis via the vascular endothelial growth factor (VEGF) pathway, has proven efficacy in extending overall survival (OS) (Sandler et al, 2006) and progression-free survival (PFS) (Sandler et al, 2006; Reck et al, 2009) when added to platinum-doublet chemotherapy as first-line treatment for advanced non-squamous NSCLC. These pivotal studies included mainly Caucasian patients, however subgroup analyses in Asian patients also reported efficacy of the first-line Bv+CP regimen (Reck et al, 2009). The BEYOND study was initiated to confirm efficacy in a Chinese population.
Patients aged ≥18 years with histologically or cytologically confirmed, locally advanced, metastatic or recurrent advanced non-squamous NSCLC and an ECOG performance status of 0–1 were randomised 1:1 to receive CP (paclitaxel 175mg/m i.v. and carboplatin AUC6 i.v. on day 1 of each 3-week cycle for up to 6 cycles), plus either Pl or Bv 15mg/kg i.v. on day 1 of each cycle, until progression, unacceptable toxicity, withdrawal of patient consent or death. Patients had no prior treatment for advanced NSCLC. Patients were stratified by gender, smoking status and age. The primary endpoint was PFS in the intent-to-treat (ITT) population; secondary endpoints included objective response rate (ORR), OS, exploratory biomarkers and safety. Collection of blood samples for biomarker analyses was mandatory (at baseline, every two cycles during treatment, at progression, and 4–6 weeks post-progression); tissue samples were optional.
276 patients were randomised into the study, 138 to each arm. Baseline characteristics were similar in both treatment groups. PFS was prolonged with Bv+CP versus Pl+CP: hazard ratio 0.40 (95% CI 0.29–0.54); median 9.2 versus 6.5 months; p<0.0001 (ITT population). ORR was also improved with the addition of Bv to CP: 54.4% versus 26.3% with Pl+CP. Disease control rate was 94.4% versus 88.7% with Bv+CP and Pl+CP, respectively. Median duration of response was 8.0 months with Bv+CP versus 5.3 months with Pl+CP. OS data are not yet mature. Safety data were similar to previous studies of Bv+CP in NSCLC; no new safety signals were observed. Treatment discontinuation due to adverse events was 18.4% (Bv+CP) and 15.0% (Pl+CP). Treatment-related deaths were low in both arms (Bv+CP: 2.2%; Pl+CP: 0.0%). Detailed safety data and biomarker analyses will be reported.
This study confirms that the addition of bevacizumab to first-line platinum-based chemotherapy appears to provide similar PFS benefits in Chinese patients with advanced non-squamous NSCLC compared with global populations. No new safety concerns were reported.
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P3.10 - Poster Session 3 - Chemotherapy (ID 210)
- Event: WCLC 2013
- Type: Poster Session
- Track: Medical Oncology
- Presentations: 1
- Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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): G. Chen
Docetaxel (75mg/m) has been reported as first-line and maintenance treatment for Western population with advanced NSCLC. Different doses of docetaxel (60mg/m) 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).
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.
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.
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.