Comparative efficacy of chemoimmunotherapy versus immunotherapy alone in the front-line treatment of advanced non-small cell lung cancer: A systematic review and network meta-analysis.

Abstract

9552 Background: Immune checkpoint inhibitors (ICI) and combination chemotherapy (chemo) plus ICI (Chemo-ICI) have been shown in RCTs to have improved OS compared to chemo in the 1L treatment of advanced NSCLC. However, the benefit of chemo-ICI compared with ICI alone is unknown. Methods: Systematic review using MEDLINE, Embase and Cochrane CENTRAL was done to identify relevant studies up to December 2019. Phase 3 RCTs that evaluated the efficacy of 1L ICI or chemo-ICI and reported outcomes stratified by PD-L1 status (<1%, 1-49%, ≥50%) were included. ICI was defined as single-agent PD-1 axis inhibitor or dual checkpoint blockade with PD-1 axis inhibitor plus CTLA-4 inhibitor. Comparison for PD-L1<1% included chemo-ICI vs ipi/nivo and for PD-L1 1-49% and PD-L1>50% included chemo-ICI vs ipi/nivo or single-agent ICI. OS, PFS, and ORR were extracted. Network meta-analysis (NMA) was done in Bayesian random-effects regression models. Results: Ten phase 3 RCTs (7971 screened) involving 7,218 patients assigned to ICI (pembro or atezo or ipi/nivo) or chemo-ICI (platinum-doublet + atezo, pembro, or nivo) were included. In PD-L1 <1% patients, NMA comparing chemo-ICI with ipi/nivo failed to show a statistically significant difference in OS, PFS or ORR. In PD-L1 1-49% patients, there was no significant difference between chemo-ICI vs ICI in OS or ORR; PFS could not be analyzed due to lack of available data. In PD-L1 >50% patients, chemo-ICI was associated with improved PFS and ORR compared to ICI alone, but without any OS difference (Table). Conclusions: Although the addition of chemo to ICI appears to improve ORR and PFS in PD-L1 ≥50% patients when compared to ICI alone, chemo-ICI does not confer an OS benefit in the 1L treatment of NSCLC patients regardless of PD-L1 status. Prospective trials comparing chemo-ICI, ICI monotherapy, and combination ICI are needed to confirm these findings. OS, PFS and ORR with chemo-ICI vs ICI. [Table: see text]