Cancer cachexia as a determinant of efficacy of first‑line pembrolizumab in patients with advanced non‑small cell lung cancer

Abstract

Pembrolizumab, either as a type of monotherapy or in combination with cytotoxic anticancer agents, is effective in the treatment of advanced non-small cell lung cancer (NSCLC). However, the development of cancer cachexia may adversely affect anticancer drug therapy. The present study investigated the effect of cancer cachexia on clinical outcomes in patients with advanced NSCLC who received first-line pembrolizumab. The data of patients with advanced NSCLC receiving first-line monotherapy or combination therapy with pembrolizumab were retrospectively analyzed. The primary endpoint was time to treatment failure (TTF), and the secondary endpoints were overall survival (OS) and incidence of adverse events (AEs). Clinical outcome was compared between patients with and without cancer cachexia. A total of 53 patients were analyzed. Among all patients, median TTF and OS were significantly shorter in patients with cancer cachexia than in those without [TTF: 5.8 vs. 10 months; hazard ratio (HR): 2.13; 95% confidence interval (CI): 1.07-4.24; P=0.016; OS: 12.1 months vs. not reached; HR: 5.85; 95% CI: 2.0-17.1; P=0.001]. In addition, TTF in the pembrolizumab monotherapy group was significantly shorter in patients with cancer cachexia than in those without, but no significant difference was detected in patients receiving pembrolizumab combination therapy. The incidence of AEs did not significantly differ between patients with and without cancer cachexia, except with regard to hypothyroidism. In conclusion, although cancer cachexia is prognostic of a poor outcome in patients with advanced NSCLC who receive first-line pembrolizumab, cancer cachexia might not affect therapeutic efficacy in combination therapy with pembrolizumab and cytotoxic anticancer agents.

Pretreatment albumin is a prognostic and predictive biomarker for response to atezolizumab across solid tumors

“…This idea is further supported by the finding that tumor‐induced cytokines (in particular IL‐6) can inhibit hepatic ketogenesis and the resulting metabolic stress increases plasma corticosteroid levels which inhibit immunotherapy in mice 21 . Our findings are also consistent with previous reports that cancer cachexia is prognostic only in ICI‐treated patients but not in chemo‐ICI combination treatment 22 …”

“…21 Our findings are also consistent with previous reports that cancer cachexia is prognostic only in ICItreated patients but not in chemo-ICI combination treatment. 22 A possible factor driving the prognostic value of albumin is cancer-induced inflammation and cachexia. There is a significant negative correlation between albumin and CRP (correlation coefficient À 0.46 in the pooled OAK and IMvigor trials), suggesting that hypoalbuminemia in cancer patients occurs in the context of chronic inflammation.…”

Low albumin status accompanies multi-layered immunosuppressive phenotypes in metastatic breast cancer patients

“…Such disruption includes rewired systemic metabolism and corruption in immunity and is clinically called cancer cachexia 1, 2, 3, 4, 6 . Disrupted homeostasis in patients generally leads to reduced quality of life and lowered efficacy of anti-cancer therapies including anti-cancer immunotherapy 7, 8 . Given the impacts of such cancer-induced disruption on a patient’s life and treatment strategies, it has been demanded to develop novel therapeutics that can mitigate cancer’s adverse effects on the host 1, 2 .…”

Progressive, multi‐organ, and multi‐layered nature of cancer cachexia

“…Indeed, we do not have specific molecular markers to define cancer cachexia. Cancer cachexia eventually reduces the quality of life and treatment efficacy and increases medical costs (i.e., financial toxicity) in patients 3–5 . Despite the well‐known negative impacts of cancer cachexia on patients, assessment and management of cancer cachexia is limited and in need of further development 1,2 …”

“…Cancer cachexia eventually reduces the quality of life and treatment efficacy and increases medical costs (i.e., financial toxicity) in patients. [3][4][5] Despite the well-known negative impacts of cancer cachexia on patients, assessment and management of cancer cachexia is limited and in need of further development. 1,2 The current definition of cancer cachexia neither provides a comprehensive picture of cancer-induced host pathophysiology nor…”