Identification of Hidden Cachexia Subgroup in PD-L1-High NSCLC: Comparative Analysis of the AWGC vs. Fearon Criteria

Cancer cachexia, frequently observed in patients with non-small cell lung cancer, is associated with reduced immunotherapy efficacy and poor prognosis. Despite the Fearon criteria being widely used to define cachexia, its relevance in Asian populations remains uncertain. Recently, the Asian Working Group for Cachexia (AWGC) proposed novel diagnostic criteria adapted for Asian body compositions. However, it remains unclear whether the outcomes or predictive value for immunotherapy differ between the AWGC and Fearon definitions. In addition, the AWGC-specific cachexia subgroup, previously regarded as noncachexia under Fearon's definition, has not been fully characterized.

We retrospectively analysed 411 Japanese patients with advanced PD-L1-high non-small cell lung cancer who received first-line PD-1/PD-L1 monotherapy or chemoimmunotherapy. Survival outcomes and clinical and nutritional indices were compared using both the AWGC and Fearon criteria. The patients were subsequently classified into three groups: (1) noncachexia, (2) A-only cachexia (meeting only the AWGC criteria), and (3) A+F cachexia (meeting both criteria). The small subgroup meeting only Fearon's criteria (n = 13) was excluded from analysis.

Per the AWGC definition, 168 patients (40.9%) were classified as having cachexia compared to 62 (15.1%) according to the Fearon definition. AWGC-defined cachexia was associated with shorter overall survival (OS) (18.2 vs. 48.5 months, adjusted HR 1.539, p = 0.003), while progression-free survival (PFS) under PD-1/PD-L1 inhibitor therapy or chemoimmunotherapy showed a nonsignificant trend (7.1 vs. 13.0 months, adjusted HR 1.253, p = 0.072). Fearon-defined cachexia similarly predicted worse OS (18.4 vs. 37.7 months, adjusted HR 1.743, p = 0.002) but not PFS (5.9 vs. 11.4 months, adjusted HR 1.326, p = 0.081). In the three-group comparisons, the A-only cachexia group (n = 119) showed intermediate characteristics: Compared with the noncachexia group, they had lower BMI, higher C-reactive protein and poorer nutritional indices (prognostic nutritional and geriatric nutritional risk indices); compared with the A+F cachexia group, they had higher BMI, lower C-reactive protein and better nutritional indices. The PFS in the A-only cachexia group was comparable with that in the noncachexia group; however, the OS was significantly shorter (21.8 vs. 48.5 months, p = 0.0002). Compared with the A+F cachexia group, the A-only cachexia group showed no significant differences but demonstrated a favourable trend toward better PFS (adjusted HR 0.72, p = 0.096) and OS (adjusted HR 0.66, p = 0.051).

The AWGC and Fearon criteria demonstrated comparable prognostic values. The A-only cachexia subgroup, previously regarded as noncachexia, retained responsiveness to immunotherapy but exhibited significantly shorter survival, underscoring its clinical relevance as a previously unrecognized at-risk group.