Real-World Effectiveness of Immune Checkpoint Inhibitors with or without Chemotherapy in Metastatic NSCLC

Despite advances in the use of immune checkpoint inhibitors (ICIs) to treat patients with non–small-cell lung cancer (NSCLC), only a subset of patients achieves the desired clinical benefit.1 Thus, there is an increasing interest in combining ICIs with other therapeutic modalities, including chemotherapy.1 However, the benefit in real-world practice of combining ICIs with chemotherapy compared with ICI monotherapy in patients with NSCLC is not well-established.2

This retrospective study included patients with metastatic NSCLC from a single-institution database treated with an ICI alone (pembrolizumab, nivolumab, or atezolizumab) or combined with platinum-based chemotherapy between January 2014 and February 2020. The study’s primary outcomes were clinical progression-free survival (PFS) and overall survival. First-line treatment outcomes were analyzed using propensity score adjustment for clinical and sociodemographic characteristics.2

A total of 1139 patients (54% male; median age, 64.9 years) were included in the study. Adenocarcinoma histology, smoking history, higher PD-L1 expression, and lower metastatic stage were associated with improved PFS. PD-L1 expression and smoking were associated with improved PFS only in patients with adenocarcinoma. Conversely, patients with squamous histology had shorter PFS independent of PD-L1 and smoking history.

In first-line–treated patients (n = 680), ICI combined with chemotherapy resulted in higher progression-free rates at 3 and 6 months compared with ICI monotherapy (3-month PFS, 85.2% vs 68.8%; P = .001 and 6-month PFS, 66.4% vs 52.6%; P = .008). The presentation provided overall results for ICI therapy and did not distinguish data among the 3 ICIs used. There was no difference overall in PFS or overall survival in either the full cohort or propensity matched cohort that took into account covariates. Treatment with ICI and chemotherapy concurrently compared with sequentially was associated with similar PFS (log-rank P = .12).

The investigators concluded that the addition of chemotherapy to ICIs may protect against early progression in real-world practice but does not affect long-term outcomes. Furthermore, treatment with sequential compared with concurrent ICI and chemotherapy regimens led to similar outcomes. These findings suggest that combination therapy may benefit patients at risk of early progression.


  1. Liu W, Zhang L, Xiu Z, et al. Combination of immune checkpoint inhibitors with chemotherapy in lung cancer. Onco Targets Ther. 2020;13:7229-7241.
  2. Hong L, Rinsurongkawong W, Saad M, et al. Real-world effectiveness of immune checkpoint inhibitors alone or in combination with chemotherapy in metastatic non–small cell lung cancer. Presented at: 2022 American Society of Clinical Oncology Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract 9055.

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