First-line treatment for driver gene–negative metastatic lung adenocarcinoma with malignant pleural effusion: Should chemotherapy be combined with an immune checkpoint inhibitor or bevacizumab？

Introduction: Patients with metastatic lung adenocarcinoma (MLA) and malignant pleural effusion (MPE) without driver gene mutations have a poor prognosis. None of the standard treatment strategies are recommended for such patients. We retrospectively analyzed the efficacy of the first-line treatment for this specific population: standard platinum-based doublet chemotherapy (CT), CT plus an immune checkpoint inhibitor (CT + ICI) and CT plus antiangiogenic agents (CT + Bev). Methods A total of 369 eligible patients were enrolled: CT alone (n = 201), CT + Bev (n = 83), and CT + ICI (n = 85). Treatment efficacy assessments were performed every two cycles according to the RECIST guidelines. The endpoints were overall survival (OS) and progression-free survival (PFS). Kaplan‒Meier curves and the log-rank test were used to compare OS and PFS. p  < 0.05 was the threshold of significance (statistical software: SPSS). Results The median follow-up was 11.4 months (range of 2.1–49.6 months). PFS and OS in the CT + ICI/CT + Bev cohort were significantly longer than those in the CT group (PFS: 7.7/7.4/4.6 months, p  = 0.001; OS: 18.5/17.8/10.9 months, p  < 0.001, respectively). CT + Bev had better PFS and OS than CT + ICI/CT in PD-L1 < 1% patients (PFS: 8.4/4.8/4.8 months, p  = 0.029; OS: 15.5/12.9/9.8 months, p  = 0.002). Among patients with PD-L1 1–49%, CT + ICI led to a longer PFS and OS (PFS: 8.8/6.4/4.2 months, p  = 0.002; OS: 34.1/21.0/11.5 months, p  = 0.049). In the cohort with PD-L1 ≥ 50%, CT + ICI was still the best first-line treatment (PFS: 19.9/9.4/8.0 months, p  = 0.029; OS: 30.2/15.5/13.0 months, p  = 0.034). Conclusion In driver gene–negative MLA with MPE, CT + Bev or ICI better controlled MPE and significantly prolonged survival compared to chemotherapy alone. PD-L1 expression (negative/positive) might be a key factor influencing the choice of CT plus Bev or ICI.