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  MTE 30 - Cachexia (Ticketed Session) (ID 82)

  • Event: WCLC 2015
  • Type: Meet the Expert (Ticketed Session)
  • Track: Palliative and Supportive Care
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2015, 07:00 - 08:00, 702+704+706

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    MTE30.02 - Cachexia (ID 2019)

    07:30 - 08:00  |  Author(s): J. Crawford
    • Abstract
    • Presentation

    Abstract:
    An international consensus group has defined cancer cachexia as “a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment”.[1] Fifty percent of patients with lung cancer have muscle wasting at diagnosis and this muscle loss increases throughout their disease course. Metabolic changes associated with cachexia lead to decreased protein stores, altered metabolism, and impaired immunity which clinically can be associated with anorexia and fatigue, weakness, and decreased physical performance. Cancer patients with muscle wasting are less able to tolerate chemotherapy, have worse treatment outcomes, loss of independence and overall shorter survival. Effective prevention and treatment strategies are needed. Although muscle wasting is central to the process of cachexia, our clinical diagnostic criteria are largely based on weight. Standard definitions for cancer cachexia include either weight loss > 5% of body weight or a body mass index (BMI) of < 20 kg/m[2] with 2% weight loss. More exact measurements of muscle and muscle wasting can be made through imaging techniques assessing lean body mass (LBM). Dexascan has been used to evaluate LBM, but is not routinely used in clinical practice currently. A very promising technique involves the use of standard computerized tomography in conjunction with a software program which accurately delineates skeletal muscle from adipose tissue, with excellent correlation with other techniques.[2] Application of this technique to a large population of patients with advanced lung and GI cancer has demonstrated a high prevalence of muscle wasting (sarcopenia) in patients with a BMI <20, but also documents a prevalence of sarcopenia of 40-60% in patients with normal BMI. At least 20% of patients with an elevated BMI also have muscle wasting (sarcopenic obesity). Studies in this population with sarcopenia regardless of baseline weight have shown increased toxicity of chemotherapy treatments, shorter time to tumor progression and decreased overall survival. Despite the frequency and severity of cancer cachexia, broad based accepted clinical practice guidelines are limited. The European Palliative Care Research Collaborative consensus recommendations[3 ]include enteral nutritional therapy, nutritional counseling, physical therapy, and psychotherapeutic interventions for quality of life benefit. However, specific pharmacologic therapies, to date, have had little established benefit. For example, Megesterol stimulates appetite and weight gain in some patients, but without an increase in muscle mass, and has significant toxicity regarding venous thromboembolic events. The most effective strategy would be effective anticancer therapy. However, in advanced cancer where our treatments may only be partially effective or ineffective, toxicities are frequent and add to the overall wasting syndrome. Improved biologic understanding of muscle wasting has led to new therapeutic approaches that are under development. One category of agents interferes with biologic signaling and cytokines that may lead to muscle atrophy, including myostatin/activan inhibitors, anti-TNFa and anti-IL6 agents, among others. Several of these agents are in early phase clinical trials. A second approach has been to target pathways that directly stimulate hypertrophy of muscle. Two of these agents have been studied in phase 3 trials in advanced lung cancer patients, enobosarm and anamorelin. Enobosarm, a selective androgen receptor modulator, has been developed to have direct action on muscle, but without androgenic effects on prostate or virilization. Phase 2 trials have shown a clear increase in LBM and physical function, leading to two randomized phase 3 trials in patients with advanced lung cancer receiving chemotherapy. These studies have shown a clear impact on improvement in LBM in both trials, but an inconsistent effect on function as measured by stair climb power between the 2 studies.[4] As predicted by the mechanism of action, no change in appetite or body weight was noted. A second approach for muscle hypertrophy is Anamorelin, a ghrelin receptor agonist. Ghrelin stimulates appetite, increase in body weight and body mass and metabolism. Randomized phase 3 trials of Anamorelin in advanced lung cancer patients have demonstrated an increase in body weight, along with LBM, but no improvement in functional assessment as measured by hand grip strength.[5] Quality of life improvements have also been seen in the study population with Anamorelin. Clinical trial results of both enobosarm and Anamorelin will be reviewed and compared in more detail, as well as potential implications for future development of these and other agents, leading to more effective therapeutic interventions for patients with cancer cachexia in the future. References Ferron K, et al. Lancet Oncol. 12:485-495, 2011. Prado C, et al. Lancet Oncol. 9:629, 2008. European Palliative Care Research Collaborative, 2011, www.epcrc.org. Crawford, J. J Clin Oncol 32:5s, 2014 (suppl; abstr 9618). Temel J, Abernethy A, et al. ASCO Proceedings, Abstract 9500, 2015.
    
    

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