OBJECTIVES: NSCLC is often diagnosed at an advanced or metastatic stage, however those who progress on first-line (1L) or subsequent treatment lines have limited options. This SLR aimed to identify evidence on the efficacy and safety of treatments for patients with metastatic NSCLC who progressed after platinum-based chemotherapy and anti-programmed cell death protein 1 (PD-1)/programmed cell death ligand (PD-L1) antibodies received in combination or sequentially.

METHODS: MEDLINE, Embase, Cochrane and Database of Abstracts of Reviews of Effect databases were searched in June 2023, supplemented with grey literature and SLR bibliography hand-searches. Eligible articles were interventional or observational studies of pharmacological interventions for metastatic NSCLC. The quality of extracted publications was assessed using the University of York’s Centre for Reviews and Dissemination or ROBINS-I tool.

RESULTS: Of 11,995 records retrieved, 54 unique studies were included. Median overall survival (OS) (n=37) ranged from 3.4 (any third-line [3L] treatment following docetaxel+ramucirumab) to 22.8 months (durvalumab+ceralasertib); it was not estimable in 5 studies. In most studies, statistical analyses for OS were not reported (n=34), or were not significant (n=4). Only 3 studies reported significant differences (p<0.05) in OS between treatments; including pembrolizumab+ramucirumab versus standard of care. Median progression-free survival (n=35) ranged from 1.4 (durvalumab+olaparib; durvalumab+oleclumab) to 12.3 months (docetaxel+ramucirumab); it was not estimable in 1 study (platinum/non-platinum-based chemotherapy). Overall objective response (n=31) ranged from 0% (multiple treatments including durvalumab+danvatirsen) to 100% (3L single-agent chemotherapy). Discontinuations due to adverse events (AEs; n=14) ranged from 0% (atezolizumab) to 40% of patients (nintedanib+docetaxel). The most reported severe AEs were fatigue (n=10) and anaemia (n=9). Patient-reported outcomes data were reported in 2 studies.

CONCLUSIONS: Outcomes with current treatments after progression on platinum-based chemotherapy and anti-PD-1/PD-L1 inhibitors remain poor, highlighting an unmet medical need in the metastatic NSCLC 1L+ population.