A Systematic Literature Review (SLR) of Real-World Evidence (RWE) on the First-Line Treatment of Advanced, Metastatic, or Recurrent Non-Small Cell Lung Cancer (NSCLC) With Immunotherapy

OBJECTIVES: The objective of this SLR was to conduct a review of RWE published since 2016 regarding the first-line treatment of advanced, metastatic, or recurrent NSCLC with existing immunotherapies.

METHODS: Database searches were conducted in March 2023, supplemented by searches of congresses since 2019, clinical trial registries and the reference lists of relevant SLRs. Due to the large volume of evidence identified and to ensure the most relevant evidence was included in the review, journal articles and conference proceedings published after 2019 and 2020, respectively, were prioritized. We present a narrative synthesis of clinical efficacy outcomes, due to limited reporting of statistical analyses.

RESULTS: After evidence prioritization, 131 publications reporting on 105 unique studies were included in the SLR. The most reported outcome was overall survival (OS) (n=91 studies), followed by progression-free survival (PFS) (n=76) and objective response rate (n=51). Included studies investigated pembrolizumab as monotherapy (n=86) or in combination with platinum doublet chemotherapy (PDC; n=29), with limited studies investigating atezolizumab plus PDC (n=2). No RWE data were identified for nivolumab.

Median OS ranged from 2.9 to 47.1 months and median PFS ranged from 3.0 to 22.6 months in patients with NSCLC with programmed cell death ligand 1 (PD-L1) ≥50% treated with pembrolizumab monotherapy. Across studies, median OS (n=7, any PD-L1 level) and PFS (n=3, PD-L1 ≥50%) were higher for patients treated with pembrolizumab combination therapy compared to pembrolizumab monotherapy. While no clear relationship between treatment efficacy and tumor histology was observed, median PFS and OS improved with increased PD-L1 expression levels for both pembrolizumab mono- and combination therapy.

CONCLUSIONS: Although a substantial amount of RWE was identified regarding the first-line use of pembrolizumab for patients with advanced or metastatic NSCLC, future RWE data with longer-term follow-up are warranted to capture the evolving evidence for more recently approved immunotherapies.