Efficacy of immune checkpoint inhibitors rechallenge and metronomic cyclophosphamide with or without bevacizumab in metastatic nonsmall cell lung cancer.

Objective: The present study aims to evaluate the efficacy of immune checkpoint inhibitor (ICI) rechallenge in combination with metronomic cyclophosphamide, with or without bevacizumab, in patients with metastatic nonsmall cell lung cancer (NSCLC) and to investigate the clinical characteristics associated with the response to the therapy.

Materials and methods: The study included 43 patients with metastatic NSCLC who responded to ICIs for ≥4 months and subsequently experienced disease progression. The patients then underwent ICI rechallenge along with either oral cyclophosphamide daily alone (n = 24) or cyclophosphamide and bevacizumab (n = 19).

Results: Combining ICI with cyclophosphamide resulted in an objective response rate (ORR) of 16.7%, disease control rate (DCR) of 75.0%, median progression-free survival (PFS) of 5.8 months, and overall survival (OS) of 15.4 months. Oral cyclophosphamide and bevacizumab cohort achieved an ORR of 26.3%, a DCR of 78.9%, a PFS of 6.8 months, and an OS of 17.6 months. No treatment-related adverse events resulted in the discontinuation of the study therapy in either cohort. Multivariate analysis demonstrated that the absence of an objective response to initial ICIs (OS: P = 0.016), poor Eastern Cooperative Oncology Group Performance Status (ECOG PS) (PFS: P = 0.017, OS: P = 0.032), and a neutrophil-to-lymphocyte ratio (NLR) ≥ 3.8 (PFS: P = 0.004, OS: P = 0.007) were negative predictors of rechallenge therapy.

Conclusion: The combination showed promising antitumor activity and a well-tolerated safety profile in patients with ICI-pretreated NSCLC. Furthermore, ECOG PS 0-1, objective response, and NLR ≤ 3.8 were predictive of the efficacy of the study therapy.