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O02 - NSCLC - Combined Modality Therapy I (ID 111)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Combined Modality
- Presentations: 1
- Moderators:W.E.E. Eberhardt, C.J. Langer
- Coordinates: 10/28/2013, 10:30 - 12:00, Parkside Ballroom B, Level 1
O02.02 - Tecemotide (L-BLP25) in unresectable stage III non-small cell lung cancer in the phase III START study: Further endpoint and exploratory biomarker results (ID 2779)
10:30 - 12:00 | Author(s): K. Horwood
The phase III START study evaluated the mucin 1 (MUC1) antigen-specific cancer immunotherapy tecemotide (L-BLP25) vs. placebo in patients with stage III unresectable non-small cell lung cancer (NSCLC) who did not progress following initial chemo-radiotherapy (chemo/RT). The primary objective of overall survival (OS) prolongation was not met, however, pre-defined subgroup analyses revealed a clinically meaningful prolongation of survival with tecemotide in patients previously treated with concurrent chemo/RT (p=0.016). Sensitivity analyses suggested the observed treatment effect may have been under-estimated due to a clinical hold, which resulted in a median suspension of recruitment and investigational treatment of about 4.4 months. Tecemotide was well tolerated and no safety concerns were identified.
From January 2007 to November 2011, 1513 patients with unresectable stage III NSCLC and stable disease or objective response following initial chemo/RT were randomized (2:1, double-blind) to subcutaneous tecemotide (806 µg lipopeptide) or placebo, weekly for 8 weeks and then 6-weekly until disease progression or withdrawal. A single dose of cyclophosphamide (300 mg/m2) or saline was given 3 days prior to first tecemotide/placebo dose. Primary endpoint, OS, and secondary endpoints progression-free-survival (PFS) and time-to-treatment-failure (TTF) used a Cox proportional hazards regression model adjusting for randomization strata. While RECIST 1.0 had to be observed for determination of disease progression, there was no formal imaging schedule to determine disease progression; this was done according to institutional practice. Exploratory analyses were done for treatment interaction for HLA-A02, -DRB4 and -B08. Baseline peripheral blood anti-nuclear antibodies (ANA), serum MUC1 (sMUC1), lymphocyte count and neutrophil:lymphocyte ratio (NLR) currently are being explored.
The primary analysis population (N=1239) was defined prospectively to account for the clinical hold and prospectively excluded 274 patients randomized within 6 months prior to onset of the hold. Median PFS was 9.6 months with tecemotide vs. 7.7 months with placebo (HR 0.865, 95%CI 0.755–0.990, p=0.036). In keeping with OS data, tecemotide treatment effects on PFS were more pronounced in patients treated with concurrent chemo/RT (N=806; HR 0.826, 95%CI 0.696–0.980, p=0.029) vs. sequential chemo/RT (N=433; HR 0.947, 95%CI 0.756–1.187, p=0.638). Median TTF was 8.9 months with tecemotide vs. 7.2 months with placebo (HR 0.887, 95%CI 0.777–1.012, p=0.075). A prolongation of TTF with tecemotide was seen in patients with prior concurrent chemo/RT (HR 0.844, 95%CI 0.715–0.996, p=0.045), which was absent in the subgroup with prior sequential chemo/RT (HR 0.977, 95%CI 0.784–1.217, p=0.835). Detailed biomarker results will be presented.
While the primary endpoint of prolongation of OS was not met, secondary endpoints PFS and TTF support the previously-reported finding of a more favorable effect of tecemotide in patients treated with concurrent but not sequential chemo/RT. Any potential further clinical investigation of tecemotide in locally advanced NSCLC should focus on patients following concurrent chemo/RT therapy.
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P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)
- Event: WCLC 2013
- Type: Poster Session
- Track: Biology
- Presentations: 1
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
P1.06-013 - Detection of Circulating Tumour Cells in Advanced Non-Small Cell Lung Cancer (ID 1492)
09:30 - 16:30 | Author(s): K. Horwood
The aim of the study was to determine whether circulating tumour cells (CTCs) can be detected and whether they provide predictive or prognostic information in a cohort of patients with locally advanced and metastatic non-small cell lung cancer (NSCLC).
Participants with locally advanced or metastatic NSCLC had blood samples collected and analysed for circulating tumour cells with the CellSearch® platform at baseline, prior to their third cycle of chemotherapy and two weeks following treatment.
Of thirty-four participants, circulating tumour cells were detected in 15 (44%). Ten out of 19 adenocarcinomas had detectable CTCs. Three of nine squamous cell carcinomas had detectable CTCs. Two of six NSCLC “not otherwise specified” had detectable CTCs. Of the 15 detected CTC cases, 10 were stage IV NSCLC. No significant associations have been seen to date with histology type, stage, performance status, age at diagnosis, gender, history of weight loss at presentation, time to progression or overall survival.
Circulating tumour cells can be detected in advanced non-small cell lung cancer. These results are intriguing and require further investigation - plans are underway to extend the study to a larger sample size to determine if there is any prognostic or predictive value to circulating tumour cell detection.