Predicting the efficacy of first-line immunotherapy by combining cancer cachexia and tumor burden in advanced non-small cell lung cancer

Background: Cancer cachexia and tumor burden predict efficacies of programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and chemotherapy or pembrolizumab in non-small cell lung cancer (NSCLC). There are no predictive models that simultaneously assess cancer cachexia and tumor burden. Methods: In the present retrospective study, we reviewed the medical records of patients with advanced NSCLC who received cancer immunotherapy as first-line systemic therapy. Clinical immune predictive scores were defined according to multivariate analysis of progression-free survival (PFS) and overall survival (OS). Results: A total of 157 patients were included in the present study (75 treated with PD-1/PD-L1 inhibitors + chemotherapy; 82, pembrolizumab monotherapy). Multivariate analysis for PFS revealed that PD-L1 tumor proportion scores <50%, a total target lesion diameter ≥76 mm, and cancer cachexia were independently associated with poor PFS. Multivariate analysis for OS revealed that ≥4 metastases and cancer cachexia were significantly associated with poor OS. In the immune predictive model, the median PFS was 21.7 months in the low-risk group (N = 41); 7.6 in the medium-risk group (N = 64); and 3.0 in the high-risk group (N = 47). The median OS were not reached, 22.4 and 9.1 months respectively. Our immune predictive model was significantly associated with PFS (p < 0.001) and OS (p < 0.001). Conclusion: We proposed the immune predictive model, including tumor burden and cancer cachexia, which may predict the efficacy and survival outcome of first-line immunotherapy in advanced NSCLC.