Tocilizumab for Advanced Non‐Small‐Cell Lung Cancer With Concomitant Cachexia: An Observational Study

Abstract

ABSTRACT Background Cancer cachexia significantly contributes to morbidity and mortality in patients with non‐small‐cell lung cancer (NSCLC). Inflammatory pathways mediated by interleukin‐6 (IL‐6) play a crucial role in the development of cancer cachexia. This study aimed to investigate the use of tocilizumab in the management of NSCLC with coexisting IL‐6‐elevated cachexia. Methods In this retrospective study, data were collected from patients with NSCLC and concurrent IL‐6‐elevated cachexia who received either tocilizumab plus antitumour therapy or antitumour therapy alone. The primary endpoints were overall survival (OS) and improved modified Glasgow Prognostic Score (mGPS) at Week 12. The secondary endpoints included changes from baseline over 12 weeks in body weight, albumin, C‐reactive protein (CRP) and mGPS. Qualitative improvements in patient self‐rated appetite and fatigue were reported as exploratory analysis. Results The study included 49 patients diagnosed with NSCLC and IL‐6‐elevated cachexia, Eastern Cooperative Oncology Group performance status of 2–4. Of these, 26 received tocilizumab in combination with antitumour therapy, and 23 received antitumour therapy alone. The majority of these patients were male (87.8%). Baseline characteristics were almost identical between the two groups. The tocilizumab group demonstrated a significantly longer median OS compared to the control group (15.1 vs. 3.2 months; hazard ratio 0.18, 95% confidence interval 0.08–0.38; p < 0.001). The rate of patients surviving with mGPS improvement at Week 12 was significantly higher in the tocilizumab group than in the control group (risk difference 0.88, 95% confidence interval 0.75–1.00; p < 0.001). Over the 12‐week period, significant improvements were observed in body weight, albumin, CRP and mGPS in the tocilizumab group compared to the control group (body weight: 5.15 ± 0.53 kg vs. −5.69 ± 0.76 kg, p = 0.041; albumin: 5.89 ± 0.70 g/L vs. −2.97 ± 0.71 g/L, p < 0.001; CRP: −91.50 ± 7.15 mg/L vs. 9.47 ± 13.69 mg/L, p < 0.001; mGPS: −1.61 ± 0.15 vs. 0.03 ± 0.08, p < 0.001). The tocilizumab group also displayed significantly higher rates of improvement in appetite and fatigue (both p < 0.001). The incidence of Grade 3 or higher adverse events was 34.6% in the tocilizumab group compared to 78.3% in the control group. Tocilizumab‐related adverse events were observed in three patients (11.5%), including two cases of neutropenia and one case of skin and subcutaneous tissue infection. Conclusion Tocilizumab demonstrated significant benefits in survival and various clinical parameters, including body weight, albumin, CRP, mGPS and symptom burden in patients with NSCLC and concurrent IL‐6‐elevated cachexia. Given the existing unmet medical need for effective interventions for cancer cachexia, tocilizumab may be considered as a potential treatment option.

Keywords

• cachexia
• interleukin‐6
• non‐small‐cell lung cancer
• tocilizumab