P76.89 Is it Possible to Halt Cachexia in Poor Performance Patients with Metastatic EGFR Positive Lung Cancer?

Abstract

Cachexia is a pro-inflammatory syndrome associated with weight loss. It now has a formal definition defined by Fearon et al in their landmark paper. It is common in lung cancer. It is a commonly held view that cachexia is irreversible in patients with advanced cancer. We wanted to understand whether 2 markers associated with cachexia (sarcopenia and the Glasgow Prognostic Score, GPS) are reversible on treatment, in patients with poor performance status at the time of diagnosis of metastatic EGFR positive lung cancer. Patients with significant weight loss and a poor GPS often have a poor prognosis. We identified 5 patients who fitted the following criteria: metastatic EGFR positive lung cancer, performance status 3 or 4, responded to first line tyrosine kinase inhibitor treatment. The surface area of the psoas muscles at the level of L3 were measured and recorded. A threshold for sarcopenia was defined as <390mm2. We tracked the surface area of psoas muscle during the first 6 months of treatment. GPS was used to assess inflammation. CRP ≤10 = 0 point, CRP >10 and albumin >35g/L = 1 point, CRP >10 and albumin ≤35g/L= 2 points. 5 patients were identified, all were female, whose age ranged from 50-83. All were PS 3+ at start of treatment, all had an initial response to treatment. 4 patients are currently responding at 4, 11, 13 and 18 months respectively. The fifth patient progressed after 9 months. All 5 patients had suitable images to assess the psoas muscle at L3. 4 patients were sarcopenic at baseline. 3 patients gained psoas muscle bulk in the first 2 months of treatment, with an increase of 8%, 11% and 17% in psoas surface area. 2 patients had broadly stable psoas muscle surface area during treatment. No patients had ongoing muscle loss within their first 4 months of treatment. The time between pre-treatment scan and initiation of therapy was on average 57 days (range 18-107), patients may have lost muscle surface area between their pre-treatment scan and initiation of treatment, which affects the interpretation of changes in muscle mass pre and post initiation of treatment. 2 patients had a GPS of 2, 1 of 1 and 1 of 0. 1 patient did not have a CRP measured. 1 patient’s albumin doubled from 20 to 40 within 2 months of treatment. EGFR mutation positive tumours are oncogene addicted and driven by over-activity of a specific pathway. Although our sample size is very small, our analysis suggests, in patients with EGFR+ advanced lung cancer, switching off the activity of the EGFR pathway also reduces the burden of systemic inflammation, allowing patients to halt the loss of muscle bulk while responding to treatment. In some cases treatment allows patients to increase muscle bulk. It suggests that successful anti-cancer treatment can halt cachexia and in certain circumstances, cachexia can be reversible.