Meta-analysis of Checkpoint Inhibitor Trials in Front-Line NSCLC

Immune checkpoint inhibitors (ICIs) and the combination of ICI and chemotherapy (chemo-ICI) have been shown in randomized controlled trials (RCTs) to improve overall survival (OS) compared with chemotherapy in the first-line treatment of patients with advanced non–small-cell lung cancer (NSCLC). However, the benefit of chemo-ICI compared with ICI monotherapy is unknown.

To explore this question, researchers conducted a systematic review of the medical literature using MEDLINE, Embase, and Cochrane CENTRAL to identify relevant studies that were performed through December 2019. Phase 3 RCTs that evaluated the efficacy of first-line ICI or chemo-ICI, and that reported outcomes stratified by PD-L1 expression level status (<1%, 1%-49%, ≥50%), were included in the analysis. ICI was defined as single-agent PD-1 inhibitor or dual checkpoint blockade with a PD-1 inhibitor plus CTLA-4 inhibitor. For patients with PD-L1 levels <1%, the study comparator was nivolumab plus ipilimumab (NIVO + IPI). For patients with PD-L1 levels between 1% and 49% and PD-L1 levels >50%, study comparators included NIVO + IPI and ICI monotherapy. Efficacy data included OS, progression-free survival (PFS), and overall response rate (ORR).

Among 7971 RCTs that were screened, 10 phase 3 RCTs were analyzed. These studies involved 7218 patients who were assigned to either ICI (pembrolizumab, atezolizumab, or NIVO + IPI) or chemo-ICI (platinum-doublet + atezolizumab, pembrolizumab, or nivolumab).

In patients whose PD-L1 levels were <1%, meta-analysis comparing chemo-ICI with NIVO + IPI failed to show a statistically significant difference in OS, PFS, or ORR.

In patients whose PD-L1 levels were between 1% and 49%, there was no significant difference between chemo-ICI compared with ICI monotherapy in OS or ORR. PFS could not be analyzed due to lack of available data.

In patients whose PD-L1 levels were ≥50%, chemo-ICI was associated with improved PFS (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.44-0.96), and ORR compared with ICI monotherapy. However, there was no difference in OS between chemo-ICI and ICI monotherapy (HR, 0.95; 95% CI, 0.64-1.40).

Researchers concluded that, although the addition of chemotherapy to ICI appears to improve ORR and PFS in patients whose PD-L1 level was ≥50% compared with ICI monotherapy, chemo-ICI does not confer an OS benefit in the first-line treatment of NSCLC patients regardless of PD-L1 status. Prospective trials that compare chemo-ICI, ICI monotherapy, and combination ICI are needed to confirm these findings.

Reference

Pathak R, Lopes G, Yu H, et al. 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. J Clin Oncol. 2020;38:suppl (abstract 9552).