Physical exercise at the crossroad between muscle wasting and the immune system: implications for lung cancer cachexia

Francesco Cortiula; Lizza E.L. Hendriks; Wouter R.P.H. van de Worp; Annemie M.W.J. Schols; Rianne D.W. Vaes; Ramon C.J. Langen; Dirk De Ruysscher

doi:10.1002/jcsm.12900

Table 2

The prognostic value of cachexia and sarcopenia during immune therapy

ICI (setting)	N	Study design	Cachexia/sarcopenia measure	Endpoint	Results (non‐cachectic vs. cachectic pts)
Anti PD(L)‐1 (advanced NSCLC) ⁴¹	142	Retrospective	>5% weight loss in the previous 6mo.	DCR PFS OS	59.9% vs. 41%, OR 2.60 (95% CI: 1–6.58) Non statistically different HR 6.26 (95% CI: 2.23–17.57)
Anti CTLA‐4 (advanced melanoma) ⁴²	97	Retrospective	CT SMD < 42HU if BMI < 25 kg/m² and <20 HU if BMI ≥ 25 kg/m²	PFS OS	2.7 vs. 2.4 months 17.5 vs. 5.4 months
Anti PD(L)‐1 (various cancers) ⁴³	100	Retrospective	L3SMI by CT (ROC cut‐offs)	PFS OS	7.5 months (95% CI: 2.9–10.9) vs. 3.3 months (95% CI: 2.8–5) 15.6 months (95% CI: 12–21.9) vs. 4.7 months (95% CI: 4.1–6.6)
Atezolizumab (Advanced NSCLC) ⁴⁴	1,434	Post‐hoc pooled analysis (4 phase III RCTs)	BMI (18–24.9 vs. 25–29.9 vs. >30)	PFS OS (BMI 25.0–29.9 vs. BMI < 25) OS (BMI > 30 vs. BMI < 25)	NS HR: 0.81 (95% CI: 0.68–0.95) HR 0.64 (95% CI: 0.51–0.81)
Anti PD(L)‐1 (advanced NSCLC) ⁴⁵	576	Systematic meta‐analysis (9 RCTs)	L3SMI, L3PMI.	PFS % irAEs OS	HR = 1.98 (95% CI: 1.32–2.97) RR = 0.99 (95% CI: 0.21–4.67) HR = 1.61 (95% CI: 1.24–2.10)

Abbreviations: BMI, body mass index; CTLA‐4, cytotoxic T‐lymphocyte antigen 4; DCR, disease control rate; HR, hazard ratio; HU, Hounsfield unit; irAEs, immune‐related adverse events; L3PMI, psoas muscle area at L3; L3SMI, skeletal muscle index at L3vertebra; NS, not significant; NSCLC, non‐small cell lung cancer; OS, overall survival; PD(L)‐1, programmed death ligand‐1; PFS, progression free survival; ROC, receiving operator curve; RR, risk ratio; SMD, skeletal muscle radiographic density.