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J. Crawford



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    P2.14 - Poster Session 2 - Mesothelioma (ID 196)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Mesothelioma
    • Presentations: 1
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      P2.14-002 - Validation of the CALGB and EORTC Prognostic Models for Mesothelioma Based on Multiple CALGB Trials (Alliance) (ID 922)

      09:30 - 09:30  |  Author(s): J. Crawford

      • Abstract

      Background
      Prognostic models play an important role in the design and analysis of mesothelioma treatment trials. The European Organisation for Research and Treatment of Cancer (EORTC) and the Cancer and Leukemia Group B (CALGB) prognostic models are two well-known tools to predict survival in patients with malignant mesothelioma. In this retrospective validation study, we aim to assess the performance of these two mesothelioma prognostic models for overall survival (OS) with multiple clinical trials data from CALGB.

      Methods
      Using 204 patients with malignant pleural mesothelioma, the EORTC model (Curran et al 1998) was developed using a Cox regression with white blood cell (WBC) count, ECOG performance status (PS), diagnosis, histological type, and gender as prognostic variables. Using 337 patients with malignant mesothelioma, the CALGB model (Herndon et al 1998) was developed using a cross-validated exponential regression tree with PS, age, haemoglobin (Hgb) level, WBC count, chest pain indicator, and weight loss indicator as prognostic variables. In this validation study, 602 mesothelioma patients from fifteen completed CALGB treatment trials accrued between June 1984 and August 2009 were included. As the CALGB model was developed using the seven earlier studies, 266 patients from eight recent studies were included in the validation. For the EORTC model, we analysed all studies as well as just those eight recent studies. The concordance of predicted survival times and risk scores was estimated by c-index (Harrell et al 1996). Secondary endpoint of interest includes progression-free survival (PFS). Sensitivity analysis and multiple imputations were used to handle missing data. We also compared our results with PS alone.

      Results
      (1) For OS, the EORTC model produced c-indices equal to 0.592 and 0.610 for the fifteen and eight studies respectively. For the eight recent studies, the CALGB model produced c-indices equal to 0.618 and 0.593 without and with imputation respectively. PS alone produced c-indices equal to 0.591 and 0.564 for the fifteen and eight studies respectively. (2) For PFS, the EORTC model produced c-indices equal to 0.569 and 0.598 for the fifteen and eight studies respectively. For the eight recent studies, the CALGB model produced c-indices equal to 0.585 and 0.560 without and with imputation respectively. PS alone produced c-indices equal to 0.568 and 0.553 for the fifteen and eight studies respectively. See Table 1. Figure 1

      Conclusion
      The EORTC and CALGB models perform similarly, with little improvement in prognostic ability from either compared to using PS alone. Further improvement on these existing prognostic models is warranted.

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    P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.11-026 - Results from two Phase 3 randomized trials of enobosarm, selective androgen receptor modulator (SARM), for the prevention and treatment of muscle wasting in NSCLC. (ID 2266)

      09:30 - 09:30  |  Author(s): J. Crawford

      • Abstract

      Background
      Cancer induced muscle wasting is a selective and progressive cancer related symptom that begins early in the course of malignancy. Greater than 50% of NSCLC patients have muscle wasting at diagnosis, increasing to >80% prior to death. Previous evidence suggests that a 1kg gain in lean body mass (LBM) is beneficial for increasing muscle strength. Enobosarm is a first-in-class nonsteroidal oral SARM. We report herein results for two Phase 3 enobosarm clinical trials, POWER1 (P1) and POWER2 (P2), for the prevention and treatment of muscle wasting in patients with advanced NSCLC.

      Methods
      Patients with Stage III or IV NSCLC were randomized into the trials at initiation of first-line chemotherapy based upon the chemotherapy regimen prescribed; platinum+taxane(P1, n=321) or platinum+non-taxane(P2, n=320). Patients (males and postmenopausal females ≥30y with ECOG ≤1) received either enobosarm 3mg or placebo for 5 months. LBM was measured by DXA and physical function was assessed by stair climb power (SCP) at days 84 (primary endpoint) and 147.

      Results
      Enobosarm had a significant effect on LBM at day 84 and 147 in both trials (P1:p=0.0003 and < 0.0001; P2: p=0.0227 and 0.0036 by continuous variable analyses). Additionally, a larger proportion of patients receiving enobosarm maintained or increased LBM at day 84 and 147 in both trials (P1:p=0.036 and 0.026; P2:p=0.113 and 0.013) as compared to placebo. Regardless of treatment, patients with ≥1kg increase in LBM were more likely to demonstrate ≥10% increase in SCP than patients that had lesser increases or had decreases in LBM (P1: 43.7% vs 29.3%, p=0.0250 and P2: 40.5% vs 26.5%, p=0.0321). The percentage improvement in SCP from baseline to day 84 differed significantly between patients with and without a ≥1kg increase in LBM: 9.1% vs -1.0% in P1(p=0.0022) and 7.7% vs -.0.6% in P2(p=0.0046). Importantly, patients with ≥1kg increases in LBM were more likely to demonstrate a ≥10% increase in SCP if they received enobosarm (P1: p=0.0698[trend] and P2: p=0.0335) than placebo (P1:p=0.3149 and P2:p=0.2852), suggesting that LBM increases in enobosarm-treated patients were more highly associated with SCP improvements in both trials (Figure). In general, patients that maintained or increased LBM had greater increases in SCP and survived longer (landmark analysis) regardless of treatment. The incidence of adverse events was similar between enobosarm and placebo in both trials. Figure 1

      Conclusion
      Overall, enobosarm was safe and well tolerated. Enobosarm had an unambiguous effect on muscle that may translate into improvement in physical function and survival in NSCLC patients.