Beyond Abscopal Effect: A Meta-Analysis of Immune Checkpoint Inhibitors and Radiotherapy in Advanced Non-Small Cell Lung Cancer

Abstract

Background: Immune checkpoint inhibitors (ICI) plus radiotherapy (RT) have been suggested as an emerging combination in non-small cell lung cancer (NSCLC) patients. However, little is known about the magnitude of its benefits and potential clinical predictors.

Objective: To assess the effects of this combination on the increase in overall and progression-free survival.

Data sources: The MEDLINE and CANCERLIT (1970-2020) electronic databases were searched, and the reference lists of included studies were manually searched.

Study selection: Studies were included if they were comparative studies between combination ICI-RT and ICI or RT alone in advanced or metastatic NSCLC patients. Overall survival (OS) was analyzed according to the treatment strategy.

Data extraction: Data on population, intervention, and outcomes were extracted from each study, in accordance with the intention-to-treat method, by two independent observers and combined using the DerSimonian method and Laird method.

Results: Compared to ICI or RT alone, ICI-RT significantly increased the 1-year and 3-year OS RR by 0.75 (95% CI 0.64-0.88; p = 0.0003) and 0.85 (95% CI 0.78-0.93; p = 0.0006), respectively. Furthermore, there was a statistically significant benefit on 1- and 3-year progression-free survival (RR 0.73 (95% CI, 0.61-0.87; p = 0.0005) and RR 0.82 (95% CI 0.67-0.99; p = 0.04), respectively).

Conclusions: In patients with advanced or metastatic NSCLC, combination ICI-RT increases 1- and 3-year OS and progression-free survival compared to ICI or RT alone.

Keywords: combination of immune checkpoint inhibitors and radiotherapy; immunotherapy; radiation oncology; radiation oncology and immunity.

Figure 1

Flow chart of the literature search and selection process.

Figure 2

1-year overall survival. Meta-analysis of 5 studies of ICI-RT association: 2 studies of ICI-RT vs. RT alone (a) and 3 studies of ICI-RT vs. IT alone (b). The risk ratio (RR) and 95% confidence interval (CI) for the effect of treatment on 1-year overall survival are shown on a logarithmic scale. Studies are arranged by publication year. Theelen study is a pooled analysis of two RCTs.

Figure 3

3-year overall survival. Meta-analysis of 5 studies of ICI-RT association: 2 studies of ICI-RT vs. RT alone (a) and 3 studies of ICI-RT vs. ICI alone (b). The risk ratio (RR) and 95% confidence interval (CI) for the effect of treatment on 3-year overall survival are shown on a logarithmic scale. Studies are arranged by publication year. Theelen study is a pooled analysis of two RCTs.

Figure 4

OS curve of studies included in the meta-analysis. Blue lines represent survival curves for each study. The red thick line represents the summarized survival curve with the 95% confidence bands (dashed lines) obtained using the approach of Combescure et al. with random effects.

Figure 5

1-year progression-free survival. Meta-analysis of 3 studies of ICI-RT association: 1 study of ICI-RT vs. RT alone (a) and 2 studies of ICI-RT vs. ICI alone (b). The risk ratio (RR) and 95% confidence interval (CI) for the effect of treatment on 1-year progression-free survival are shown on a logarithmic scale. Studies are arranged by publication year. Theelen study is a pooled analysis of two RCTs.

Figure 6

3-year progression-free survival. Meta-analysis of 3 studies of ICI-RT association: 1 study of ICI-RT vs. RT alone (a) and 2 studies of ICI-RT vs. ICI alone (b). The risk ratio (RR) and 95% confidence interval (CI) for the effect of treatment on 3-year progression-free survival are shown on a logarithmic scale. Studies are arranged by publication year. Theelen study is a pooled analysis of two RCTs.

Figure 7

The risk ratio of the most frequent adverse events in the association treatment group as compared to the single Table 95. confidence interval (CI) for the adverse effect rate are shown on a logarithmic scale. Adverse events are arranged by alphabetic order (all grade AE and 3–4 grade, respectively).