What is next after anamorelin?

Abstract

Purpose In spite of its relevance, treatments for the cancer anorexia and cachexia syndrome (CACS) are not available. One of the agents that recently reached phase III clinical trials is anamorelin. Its development, along with that of other agents for this indication will be reviewed here, with a focus on the gaps in the current knowledge and future directions. Recent Findings In spite of several targets showing promising results in early development, their difficulties obtaining regulatory approval underscores the need to reconsider the current strategies in drug development and the challenges in the field of CACS. Summary Further research is needed in order to meet the challenges of developing treatments for CACS. Pre-clinical studies should expand our understanding about key regulators of appetite, muscle and energy metabolism in this setting using models that can be translated reliably to humans. Clinical research efforts should focus on validating the entry criteria, endpoints, outcomes and the potential synergistic effects and interaction between different targets, nutrition and exercise interventions. Clinical meaningfulness and significance should be taken into account in the design of clinical trials. It is essential that all key stakeholders are included in the design of future strategies.

The Use of Proton Pump Inhibitors May Increase Symptoms of Muscle Function Loss in Patients with Chronic Illnesses

“…Moreover, animal data indicate that the PPI omeprazole reduces microbiota diversity. In [9], microbiota-derived formate levels were increased. Microbiota-derived formate levels have been associated with increased intestinal inflammation.…”

“…Muscle mass and muscle function are to a large extent, related. It is only recently that it has become apparent that preservation of only muscle mass without improving muscle function has no effect on quality of life and mortality rates in cancer patients [9]. Apparently, loss of muscle function is contributing to a higher extent to morbidity and mortality than loss of muscle mass.…”

“…An increase in Enterobacteriaceae can be seen in both cachectic patients and in PPI-users, which results in increased LPS production and activation of TLR4, increasing inflammatory status [9]. Moreover, animal data indicate that the PPI omeprazole reduces microbiota diversity.…”

New developments in investigational HDAC inhibitors for the potential multimodal treatment of cachexia

“…The results of these trials do not provide clear-cut evidence about anamorelin effectiveness to treat cancer cachexia. Indeed, while positive results have been reported in non-small cell lung cancer patients, the ROMANA trials have shown that while anamorelin improves body weight loss and FAACT score in lung cancer patients, it is not able to rescue the loss of hand grip strength [22] [23]. Subsequent investigations have shown that, in selected groups of patients, anamorelin also leads to improved performance status [24].…”

Cancer-associated weight loss: releasing its firm grip on negative clinical outcomes

“…The past 5 years have yielded immense disappointment in efforts to treat the cancer-associated weight loss syndrome. As reviewed by Garcia in this issue of Current Opinions in Supportive and Palliative Care , two large registration trials, which, in total, included over 1500 patients and cost an estimated $100 million, failed to achieve their primary dual endpoints [1–3]. Neither of these trials — one which tested the selective androgen receptor modulator, enobosarm, and the other of which tested the oral ghrelin mimetic, anamorelin — resulted in a prescribable agent, leading to the same stagnant conclusion that modest palliation with older agents such as progesterones and corticosteroids remains the only proven therapeutic approach for select weight-losing cancer patients with an incurable malignancy [4,5].…”