OBJECTIVES: Immuno-oncology (IO) agents have changed the standard of care for NSCLC. This study aimed to summarize the efficacy of IO therapies and chemotherapies in untreated advanced or metastatic NSCLC.

METHODS: A systematic literature review of MEDLINE, Embase, and Cochrane Library identified clinical trials that met the following criteria: 1) included adults with untreated advanced or metastatic NSCLC; 2) included an IO agent or a chemotherapy agent recommended in clinical guidelines; 3) reported efficacy outcomes; and 4) published no earlier than 2002.

RESULTS: Among 110 clinical trials identified, 99 focused on chemotherapies, with median progression-free survival (PFS) and overall survival (OS) ranging from 2.6-9.2 months and 5.9-27.3 months, respectively. Eleven IO trials (3 pembrolizumab, 4 nivolumab, 3 atezolizumab, and 1 durvalumab) were identified, of which 9 were phase I/II studies. For the IO treatment arms that had reached median PFS by data cut-off, the range was 3.6-10.3 months for IO monotherapies, 4.9-10.6 months for IO-IO combination therapies, and 4.8-13.0 months for IO-chemotherapy combinations. Only three IO studies had reached the median OS. Three studies directly compared IO therapies with chemotherapies. KEYNOTE-024 demonstrated significantly longer PFS and OS for pembrolizumab compared with chemotherapy in programmed cell death ligand-1 (PD-L1)-positive patients, while CheckMate-026 did not show superior PFS or OS for nivolumab in the PD-L1-positive population. However, there was considerable heterogeneity in PD-L1 cut-offs and the assay used between these two studies. The third study (KEYNOTE-021 Cohort G) reported significantly longer PFS for pembrolizumab plus chemotherapy in non-squamous NSCLC irrespective of PD-L1 levels.

CONCLUSIONS: The survival benefit of chemotherapies is limited for patients with untreated advanced or metastatic NSCLC. One IO monotherapy has demonstrated significantly improved survival over chemotherapy in patients expressing PD-L1. IO combination therapies are showing great potential in all comers, but more data are needed to confirm their superiority.