Author of

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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
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12674

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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): M.S. Steiner
    • 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.