End-of-life care

Cancer cachexia: drug treatments on the horizon

The first evidence-based drug treatment that can slow the progression of wasting in cancer cachexia may soon be available in Australia, according to palliative care specialist Professor David Currow.

Speaking at an industry-sponsored session at MOGA 2019 ASM in Canberra, Professor Currow said that after years of having no effective way to manage or reverse the wasting condition in advanced cancer patients there is now the potential to access an oral ghrelin-agonist, anamorelin.

The drug, developed by Swiss-based Helsinn, has been shown in phase 3 trials to have appetite-stimulating and anabolic effects that result in increases in lean body mass and body weight when compared to placebo in cancer patients with cachexia, he told the MOGA meeting.

Professor Currow, who is Chief Cancer Officer and CEO of the Cancer Institute NSW,  said cachexia was a widespread debilitating problem that was too often dismissed by clinicians as an inevitable and unavoidable aspect of late stage cancer.

Yet while many drug treatments and nutritional interventions had proved poorly tolerated and ineffective in cancer cachexia, patients should at least be offered a nutritional assessment to identify other treatable factors such as malnutrition, Professor Currow told the meeting.

“The diagnosis of cancer cachexia is still largely a diagnosis of exclusion,” he said.

“So distinguishing clearly in our minds between starvation, cachexia and sarcopenia is really important.”

Unlike the other conditions, cachexia was caused by tumour-related systemic inflammation, metabolic dysregulation and loss of appetite resulting in loss of both lean muscle and fat mass, he said.

Muscle atrophy in cachexia led not only to weakness, fatigue and general loss of function but also to cardiovascular and respiratory impairment and loss of bowel function. The loss of lean body mass also affected response and toleration with chemotherapy

There was some evidence for multimodal nutritional supplement and exercise interventions in cancer cachexia, but tolerability and adherence levels have been poor even in highly motivated and well-supported patients in clinical trial settings, said Professor Currow.

“One of the main messages from the recent international consensus statement on cachexia is that you cannot fully reverse it with conventional nutritional support,” he said.

“How many of us have referred a patient to a dietician for high calorie, high protein supplementation? Let’s be honest we’re condemning them to these unpalatable supplements three times a day and there’s not a lot we can do to disguise it – it’s revolting, so we’ve got a fundamental challenge ahead of us,” he said

Similarly, there were major limitations with drug therapies used in an attempt to reverse weight loss such as glucocorticoids, progesterones, cannabinoids and anabolic steroids, said Professor Currow.

None of them were licensed for use in cancer cachexia and many had serious adverse effects and could be counter-productive, he warned.

Newer agents such as anamorelin and the selective androgen receptor modulator (SARM) enobosarm had shown promising effects on weight and body composition in patients with cancer cachexia, said Professor Currow.

In one trial involving 513 patients with inoperable NSCLC and cachexia, the average change in lean body mass over 24 weeks was around 3kg with anamorelin compared to 0.5kg  in a control group. The drug also appeared well tolerated with a similar 3% rate of treatment-related serious adverse events as seen with placebo.

The drug is expected to receive its world-first regulatory licensing in Japan in September and could also be imported via the TGA’s Special Access Scheme at a cost of around $400 a month

“Cachexia is a massive problem for the patients that we see every day. Ultimately we need to re-think our approach to cachexia weight loss in cancer. We’ve accepted it with a shrug of our shoulders as just an integral part of the disease process.”

“I think as we look to the future we will be looking at multimodal interventions that include exercise, adequate nutritional assessments and the new opportunities offered by pharmacological agents such as anamorelin,” he concluded.

The session was supported by Specialised Therapeutics, the local distributor of anamorelin.

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