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J.R. Pereira



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    O02 - NSCLC - Combined Modality Therapy I (ID 111)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Combined Modality
    • Presentations: 1
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      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)

      10:40 - 10:50  |  Author(s): J.R. Pereira

      • Abstract
      • Presentation
      • Slides

      Background
      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.

      Methods
      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.

      Results
      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.

      Conclusion
      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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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-034 - Weight Gain as a Prognostic Factor on Patient Outcomes<br /> In Advanced, Nonsquamous, Non-small Cell Lung Cancer (ID 1905)

      09:30 - 09:30  |  Author(s): J.R. Pereira

      • Abstract

      Background
      Patients with advanced/metastatic non-small cell lung cancer (NSCLC) have a poor prognosis and low survival rates. One of the first notable symptoms of advanced lung cancer is unexplained weight loss. We evaluated weight gain (> 5% post baseline), as an early prognostic factor for clinical outcome, in advanced nonsquamous, NSCLC patients.

      Methods
      This retrospective analysis reports on three randomized phase III studies with survival and response data from a total of 2301 advanced, nonsquamous NSCLC patients who received pemetrexed or other chemotherapy plus a platinum or targeted agent, as first-line therapy. Body weight was recorded before and after treatment by each study’s schedule. Baseline weight was defined as the last non-missing weight measure before first treatment. Post baseline weight was defined as the maximum weight measured after starting treatment. Patients were analyzed using log-rank test and adjusted Cox modeling to assess the relationship between weight gain and overall survival (OS) and progression-free survival (PFS). Logistic regression was used to assess the association between baseline covariates and post-baseline weight gain.

      Results
      Patients were a mean age of 61 years (range 26 – 86) and most were of Caucasian descent (77.0%). A majority of patients had adenocarcinoma (73.8%), were male (59.8%) with an ECOG performance status (PS) of 0/1/2 (38.5%/60.2%/1.4%). Many patients were smokers or former smokers (55.7%) with Stage IV disease (83.1 %), according to the American Joint Committee on Cancer, editions. 5/6 and had an average weight at baseline of 71.4 kg. A total of 421 (18.3%) patients had a >5% increase in weight (>5% subgroup) after baseline with a statistically significant increase in OS and PFS. Median OS was 16.7 months for patients in the >5% subgroup versus 10.7 months for patients who gained <5% weight (< 5% subgroup; [n=1880]; p<0.001). PFS was 6.9 months for the >5% subgroup versus 4.8 months for <5% subgroup; p<0.001). Differences in overall response rate (ORR = CR + PR) and disease control rate (DCR = CR + PR + SD) were also significant. ORR was 50.8% for >5% subgroup versus 25.4% for < 5% subgroup (p<0.001). DCR was 91.5% for >5% subgroup and 63.6% for <5% subgroup (p<0.001). Cox modeling revealed patients in the >5% subgroup had significantly longer survival (HR=0.56, [95% CI 0.49-0.64]; p<0.001) than patients with <5% subgroup, after adjusting for baseline age (<65 versus 65), sex, ECOG PS (0 versus 1/2), histology (adenocarcinoma versus others), and study. Similar significant results were also found for PFS. Logistic regression indicated a significant association between weight gain and age. More patients aged <65 had a >5% weight gain (p<0.001).

      Conclusion
      This exploratory analysis showed that substantial weight gain (>5%) occurred after initiation of platinum-based chemotherapy in approximately 20% of advanced/metastatic, nonsquamous NSCLC patients. There was a positive correlation between weight gain and improved, OS, PFS and response in patients treated in these phase III studies.