Incidence of pneumonitis with use of PD-1 and PD-L1 inhibitors in non-small cell lung cancer: A Systematic Review and Meta-analysis of trials

Background

PD-1/PD-L1 inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis, and differences according to type of inhibitors and prior chemotherapy use.

Methods

Medline, Embase and Scopus databases were searched up to November 2016. Rates of pneumonitis of any grade and grade 3 or higher from all clinical trials investigating nivolumab, pembrolizumab, atezolimumab, durvalumab, and avelumab as single agents in NSCLC were collected. The incidence of pneumonitis across trials was calculated using DerSimonian-Laird random effects models. We compared incidences between PD-1 and PD-L1 inhibitors, as well as between treatment naive and previously treated patients.

Results

19 trials (12 with PD-1 inhibitors [n=3232] and 7 with PD-L1 inhibitors [n=1806]) were identified. PD-1 inhibitors were found to have statistically significant higher incidence of any grade pneumonitis as compared to PD-L1 inhibitors (3.6%, 95%CI 2.4%-4.9% vs 1.3%, 95%CI 0.8%-1.9%, respectively; p=0.001). PD-1 inhibitors were also associated with higher incidence of grade 3-4 pneumonitis (1.1%, 95%CI 0.6%-1.7% vs 0.4%, 95%CI 0%-0.8%, p=0.02). Treatment naïve patients had higher incidence of grade 1-4 pneumonitis as compared to previously treated patients (4.3%, 95%CI 2.4%-6.3% vs 2.8%, 95%CI 1.7%- 4%, p=0.03).

Conclusion

There was a higher incidence of pneumonitis with use of PD-1 inhibitors as compared to PD-L1 inhibitors. Higher rate of pneumonitis was more common in treatment naïve patients.

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