Incidence of PD-1 Inhibitor–Related Pneumonitis in Patients With Advanced Cancer
abstract
This abstract is available on the publisher's site.
Access this abstract nowImportance
Programmed cell death 1 (PD-1) inhibitor-related pneumonitis is a rare but clinically serious and potentially life-threatening adverse event. Little is known about its incidence across different tumor types and treatment regimens.
Objective
To compare the incidence of PD-1 inhibitor-related pneumonitis among different tumor types and therapeutic regimens.
Data Sources
A PubMed search through November 10, 2015, and a review of references from relevant articles. For the PubMed search, the following keywords or corresponding Medical Subject Heading terms were used: nivolumab, pembrolizumab, and PD-1 inhibitor.
Study Selection
Twenty-six original articles of PD-1 inhibitor trial results were identified. Among them, 20 studies of melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma (RCC) were eligible for a meta-analysis.
Data Extraction and Synthesis
The data were extracted by 1 primary reviewer and then independently reviewed by 2 secondary reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Comparisons of the incidence were based on marginal, exact generalized linear models with generalized estimating equations.
Main Outcomes and Measures
Incidence of all-grade and grade 3 or higher pneumonitis and pneumonitis-related deaths.
Results
Twenty studies of single-tumor-type trials of PD-1 inhibitor (12 melanoma studies, 5 NSCLC studies, and 3 RCC studies) (a total of 4496 unique patients) were included in the meta-analysis. The overall incidence of pneumonitis during PD-1 inhibitor monotherapy was 2.7% (95% CI, 1.9%-3.6%) for all-grade and 0.8% (95% CI, 0.4%-1.2%) for grade 3 or higher pneumonitis. The incidence was higher in NSCLC for all-grade (4.1% vs 1.6%; P = .002) and grade 3 or higher pneumonitis (1.8% vs 0.2%; P < .001) compared with melanoma. The incidence in RCC was higher than in melanoma for all-grade pneumonitis (4.1% vs 1.6%; P < .001) but not for grade 3 or higher pneumonitis. Four pneumonitis-related deaths were observed in patients with NSCLC in the monotherapy group. Pneumonitis was more frequent during combination therapy than monotherapy for all-grade (6.6% vs 1.6%; P < .001) and grade 3 or higher pneumonitis (1.5% vs 0.2%; P = .001) in melanoma, with 1 pneumonitis-related death during combination therapy. Multivariable analyses demonstrated higher odds of pneumonitis in NSCLC for all-grade (odds ratio [OR], 1.43; 95% CI, 1.08-1.89; P = .005) and grade 3 or higher pneumonitis (OR, 2.85; 95% CI, 1.60-5.08; P < .001) and in RCC for all-grade pneumonitis (OR, 1.59; 95% CI, 1.32-1.92; P < .001) compared with melanoma. The combination therapy had significantly higher odds than monotherapy for all-grade (OR, 2.04; 95% CI, 1.69-2.50; P < .001) and grade 3 or higher pneumonitis (OR, 2.86; 95% CI, 1.79- 4.35; P < .001).
Conclusions and Relevance
The incidence of PD-1 inhibitor-related pneumonitis was higher in NSCLC and RCC and during combination therapy. These findings contribute to enhance awareness among clinicians and support further investigations to meet the clinical needs.
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Additional Info
Disclosure statements are available on the authors' profiles:
Incidence of Programmed Cell Death 1 Inhibitor-Related Pneumonitis in Patients With Advanced Cancer: A Systematic Review and Meta-Analysis
JAMA Oncol 2016 Dec 01;2(12)1607-1616, M Nishino, A Giobbie-Hurder, H Hatabu, NH Ramaiya, FS HodiFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Pneumonitis Management in PD1 Checkpoint Inhibitors for Renal Cell Carcinoma
PD1 checkpoint inhibitors have become a key class of drugs in the arsenal for advanced renal cell carcinoma. It is critical that providers who prescribe immune checkpoint inhibitors have an understanding of the toxicity profile and how to manage potentially serious side effects. It is also critical to assure good patient education prior to administering them. Pneumonitis is a well-known, potentially serious toxicity, which is relatively uncommon. This study evaluates pneumonitis associated with the use of PD1 inhibitors in several cancers, including RCC, and was designed to pool the data in order to better understand it.
This study was a meta-analysis encompassing 26 studies, 3 of which were RCC trials, and 4496 unique patients. The overall incidence of pneumonitis was 2.7% (95% CI, 1.9%–3.6%) for all grades and 0.8% (95% CI, 0.4–1.2%) for grade 3 or greater. Toxicity was generally greater with combination immunotherapy.
Presenting symptoms of pneumonitis can include new or worsening cough, chest pain, and shortness of breath. Some patients may be asymptomatic and have radiographic changes only. As providers, it is important to be familiar with the presentation and management strategies as outlined below.
Grade 1: Radiographic changes only
Grade 2: Mild to moderate symptoms or worsening from baseline
Grade 3/4: Severe symptoms, new/worsening hypoxia, or life-threating symptoms ± hospitalization