Abstract / Summary
Objective: Liver metastasis represents one of the frequent drivers for cancer-related mortality in lung adenocarcinoma. For advanced lung adenocarcinoma harboring wild-type oncogene drivers, chemotherapies in combination with immune checkpoint inhibitors (ICIs) and/or bevacizumab (named IC, BC, and IBC, respectively) are alternative first-line schemes as recommended by canonical treatment guidelines. However, due to the immunosuppressive tumor microenvironment in the liver, patients with liver metastases are less effective to ICIs. For this subpopulation, the optimal regimen is still undetermined.
Methods: In this retrospective multicenter cohort study, treatment-naïve lung adenocarcinoma patients with wild-type oncogene drivers and liver metastases were enrolled from 4 cancer centers between January 2018 and December 2023. All these patients received BC, IC, or IBC as the first-line therapies. Propensity Score Matching (PSM) was applied to balance baseline covariates. Kaplan-Meier survival analysis, log-rank tests, and Cox proportional-hazards regression were used to compare PFS and OS among groups.
Results: A total of 191 Patients were enrolled, in which 70 (36.6%) received IC treatment, 70 (36.6%) received BC and 51 (26.7%) received IBC treatment. After PSM, 135 eligible patients were selected, including 45 Patients in each group. IBC group showed a slightly higher ORR (44.4%) and significantly higher DCR (95.6%, p = 0.013) compared with BC (ORR = 37.2%, DCR = 81.4%) and IC (ORR = 38.5%, DCR = 71.8%) groups, as evaluated by the primary lung lesions. When liver metastases were used as target lesions, similar response was observed. The median progression-free survival (mPFS) in patients receiving IBC (8.48 months, 95% CI: 5.98-16.10 months) was significantly longer than those receiving BC (5.09 months, 95% CI: 3.55-7.46 months) and IC (4.86 months, 95% CI: 3.06-7.82 months) (IBC vs. BC: HR = 0.477, 95% CI: 0.295-0.772, p = 0.002; IBC vs. IC: HR = 0.479, 95% CI: 0.292-0.784, p = 0.003). IBC also showed a numerically longer OS than IC (18.99 months vs. 12.52 months; HR = 0.692, 95% CI: 0.429-1.114, p = 0.128), although this difference did not reach statistical significance. Subgroup analyses, conducted as pre-specified exploratory analyses, showed that patients with male gender, smoking history, brain metastasis, polymetastases and low PD-L1 expression (< 50%) displayed superior PFS when treated with IBC compared with their counterparts. Besides, IBC showed comparable adverse events relative to IC and BC treatments.
Conclusions: IBC treatment showed superior efficacy in oncogene wild-type lung adenocarcinoma patients with liver metastases, especially in those with male gender, smoking history, brain metastasis, polymetastases, and low PD-L1 expression.