Negative impact of cachexia during chemotherapy on survival as first-line chemotherapy for metastatic colorectal cancer.

Abstract

126 Background: Sarcopenia and muscle loss during chemotherapy (Cx) have a poor prognosis in metastatic colorectal cancer (mCRC). It is unclear whether cachexia during Cx has a survival impact. Methods: mCRC patients (pts) receiving first-line Cx at a single institution between Jan 2010 and Jun 2018 were retrospectively evaluated. Pts receiving doublet Cx with bevacizumab or anti-EGFR agents, ECOG Performance Status (PS) 0–2, and abdominal computed tomography (CT) before and after initiating first-line Cx at least once were included and classified pts into those with (cachexia group) or without (non-cachexia group) cachexia. The skeletal muscle index (SMI) was calculated from the CT cross-section area at L3 divided by the length squared. Muscle loss was defined as a < 5% reduction in the SMI. The association between muscle loss and cachexia during Cx, time to treatment failure (TTF) and overall survival (OS) was determined by univariate and multivariate analysis including muscle loss, primary tumor location, ECOG PS, number of metastatic sites, ALP, WBC, LDH, KRAS status, and BRAF status as independent variables. Results: Of 562 included pts, 185 were eligible and 69 (37%) experienced cachexia. Differences in all patient characteristics such as muscle loss, ECOG PS 2, KRAS mutant, and BRAF mutant (28%, 8%, 32%, and 10% with cachexia group and 27%, 3%, 32%, and 8% with non-cachexia group) were not significant. Median follow-up was 26.8 months. Muscle loss was not associated with TTF (13.3 vs. 15.5 months, HR = 1.05; 95% CI: 0.76–1.45, p = 0.76). OS was shorter (24.4 vs. 29.9 months, HR = 1.23; 95% CI: 0.86–1.76, p = 0.25), but the difference was not significant in univariate and multivariate analysis. However, cachexia group presented significantly shorter TTF [median TTF 11.9 vs. 16.9 m; HR 1.52, 95% CI: 1.12-2.07, p < 0.01; adjusted HR (aHR) 1.53, 95% CI: 1.12-2.11, p < 0.01] and shorter OS (median OS 21.4 vs. 34.1 m; HR 1.81, 95% CI: 1.29-2.55, p < 0.01; aHR 1.97, 95% CI: 1.38-2.81, p < 0.01) than non-cachexia group. Conclusions: Cachexia during Cx may have a negative impact on survival in pts with mCRC.

Exploring the impact of patient‐specific clinical features on osimertinib effectiveness in a real‐world cohort of patients with EGFR mutated non‐small cell lung cancer

“…Cachexia, for example, which is correlated with poor response and survival, leads to higher inflammation, reduced CYP-activity and loss of body mass, thereby changing the body distribution of osimertinib and its C min,SS . 51,52 While in a limited number of patients, Boosman et al found no obvious effect of sarcopenia on the association between osimertinib effectiveness outcomes and its C min,SS . 30 The potential impact of cachexia on the effectiveness of osimertinib has not been evaluated extensively.…”

“…In addition, other factors that could not be included in our analyses, may contribute to the lower survival seen in patients with a high osimertinib C min,SS . Cachexia, for example, which is correlated with poor response and survival, leads to higher inflammation, reduced CYP‐activity and loss of body mass, thereby changing the body distribution of osimertinib and its C min,SS 51,52 . While in a limited number of patients, Boosman et al found no obvious effect of sarcopenia on the association between osimertinib effectiveness outcomes and its C min,SS 30 .…”

Early administration of anamorelin improves cancer cachexia in patients with gastrointestinal cancer

“…Cachexia occurs in approximately 80% of patients with advanced cancer (Dewys et al 1980; Argilés et al 2014) and accounts for approximately 30% of cancer-related deaths (Tisdale 2003;Acharyya et al 2005;Fearon 2008;Tisdale 2009;Farkas et al 2013). Furthermore, up to 80% of patients with advanced gastric cancer (GC) develop cachexia (Namikawa et al 2022), as do 37-50.4% of patients with unresectable colorectal cancer (CRC) (Nozawa et al 2020;Blum et al 2010).…”