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.

Abstract

e20647 Background: PD-1/PD-L1 inhibitors show clinical activity in non-small cell lung carcinoma (NSCLC). However, these agents are sometimes associated with potentially fatal immune related pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis associated with PD-1 and PD-L1 inhibitors. In this meta-analysis, we sought to determine the overall incidence of pneumonitis, and differences by type of inhibitor and prior chemotherapy use. Methods:We systematically searched databases (PubMed-Medline, Embase, Scopus) and conference proceedings until December 2016 for clinical trials using PD-1/PD-L1 inhibitors. Rates of pneumonitis of any grade and grade 3 or higher from all phase I-III trials investigating nivolumab, pembrolizumab, atezolimumab, durvalumab and avelumab for NSCLC were collected. Only single agent PD-1/PDL-1 inhibitor trials were included. 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 naïve and previously treated patients (pts). Results: 19 distinct published 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%; p = 0.001). There was also a higher incidence of grade 3 or greater pneumonitis with PD-1 inhibitors (1.1%, 95%CI 0.6%-1.7% vs 0.4%, 95%CI 0%-0.8%, p = 0.02). Pts who received PD-1 or PD-L1 inhibitors in the front line setting experienced more grade 1-4 pneumonitis as compared to previously treated pts (4.3%, 95%CI 2.4%-6.3% vs 2.8%, 95%CI 1.7%- 4%, p = 0.03, however the rates of grade 3 or greater pneumonitis were not significantly different in treatment naïve and previously treated pts. Conclusions: Pneumonitis was more frequently associated with use of PD-1 inhibitors than PD-L1 inhibitors. There was a higher incidence of all grade pneumonitis with PD-1 inhibitors in treatment naïve patients as compared to previously treated patients.