Comparing the Rate of Pneumonitis Associated with Treatment with PD-1 and PD-L1 Inhibitors in Patients with Lung Cancer

Chicago—Treatment with the PD-1 and PD-L1 immune checkpoint inhibitors has been shown to be effective in patients with non-small cell lung cancer (NSCLC). However, treatment with these immunotherapy agents has also been associated with potentially fatal immune-related pneumonitis.


To determine if pneumonitis was more frequently associated with one form of treatment, Monica Khunger, MD, and colleagues at the Cleveland Clinic, Case Western Reserve, the University of Connecticut, and the Cleveland Clinic Taussig Cancer Institute, conducted a meta-analysis of previously published research “to determine the overall incidence of pneumonitis and differences by type of inhibitor and prior chemotherapy use.” The results of the study were presented in a publication-only abstract published in conjunction with the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.


The authors systematically searched conference proceedings and the PubMed-Medline, Embase, and Scopus databases for single-agent, phase 1-3 clinical trials published up to December 2016 that examined the use of PD-1 and PD-L1 inhibitors. They recorded the rates of pneumonitis of any grade and of grade ≥3 in all trials investigating the use of nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab for the treatment of NSCLC.


In all, they included 19 published trials (12 with PD-1 inhibitors involving 3232 patients and 7 with PD-L1 inhibitors involving 1806 patients).


Using DerSimonian-Laird random-effects models, the authors calculated the incidence of pneumonitis across trials, and compared incidences in patients treated with PD-1 and PD-L1 inhibitors. They also compared pneumonitis incidence in previously treated patients and treatment-naïve patients.


Treatment with PD-1 inhibitors was associated with a statistically significantly higher incidence of any grade pneumonitis compared with treatment with PD-L1 inhibitors (3.6%; 95% confidence interval [CI], 2.4-4.9 vs 1.3%; 95% CI, 0.8-1.9; p=0.001). The data also revealed that treatment with PD-1 inhibitors was associated with a higher incidence of grade ≥3 pneumonitis (1.1%; 95% CI, 0.6-1.7 vs 0.4%; 95% CI, 0-0.8; p=0.02).


Patients who received frontline treatment with either PD-1 or PD-L1 inhibitors experienced a higher incidence of grade 1-4 pneumonitis compared with previously-treated patients (4.3%; 95% CI, 2.4-6.3 vs 2.8%; 95% CI, 1.7- 4;, p=0.03). Rates of grade ≥3 pneumonitis were not significantly different between the groups.


Based on these results, the authors concluded that “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 compared with previously treated patients.”


Source: Khunger M, Pasupuleti V, Rakshit S, et al. 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. J Clin Oncol 35, 2017 (suppl; abstr e20647).