2019 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Poster Session
Time: Sunday June 2, 8:00 AM to 11:00 AM
Location: Hall A
Variation in the assessment of immune-related adverse event occurrence, grade, and timing.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #370)
J Clin Oncol 37, 2019 (suppl; abstr 9047)
Author(s): David Hsieh, Mary Katherine Watters, Rong Lu, Yang Xie, David E. Gerber; Univ of Texas Southwestern Med School, Dallas, TX; UT Southwestern Medical Center, Dallas, TX; The University of Texas Southwestern Medical Center, Dallas, TX
Background: Accurate assessment of treatment toxicity is critical for patient safety, balancing clinical utility, and understanding treatment impact. Given their unpredictability and heterogeneity, immune-related adverse events (irAEs) may be particularly challenging to ascertain. Our objective was to evaluate the agreement between clinicians on the occurrence, grade, and timing of irAEs, and elucidate determinants of discordance. Methods: We performed a retrospective cohort study of 52 patients with cancer treated with immune checkpoint inhibitors at a National Cancer Institute-designated comprehensive cancer center. Two medical oncologist observers used algorithm-driven manual chart review to characterize eight well-described irAEs (adrenal insufficiency, colitis, hepatitis, hyperthyroidism, hypophysitis, hypothyroidism, pneumonitis, rash). Inter-rater agreement for incidence, severity, and timing of irAEs was determined using Cohen's kappa coefficient (κ) and weighted κ with linear weights. Results: The incidence of irAEs ranged from 4-35% for observer 1 and 6-27% for observer 2, while aggregate incidence rates ranged from 8% (hypophysitis) to 40% (pneumonitis). Inter-rater agreement was generally limited for irAE incidence (κ 0.37 [hypophysitis]-0.8 [hypothyroidism]). Weighted κ similarly showed limited or poor agreement for most irAE grades (κ 0.31-0.75). Differences in the assessment of irAE time of onset ranged from 5-188 days. Rates of discordance were greater for grade 1 (39%) and grade 2 (41%) irAEs than for grade 3-4 (20%) irAEs. Multivariable analyses showed that longer therapy duration (OR 4.8, P= 0.02) and a high Charlson Comorbidity Index (OR 4.09, P= 0.03) were significantly associated with discordant irAE assessment. Conclusions: Inter-rater reliability varied among irAEs and consistently showed poor agreement for the incidence, severity, and timing of irAEs. Agreement was greater for irAEs with distinct laboratory-based definitions (eg, hypothyroidism), higher-grade irAEs, and irAEs in patients with fewer comorbidities and shorter immunotherapy duration. These findings have implications in the clinical management of patients receiving immunotherapy and in the reporting of immunotherapy clinical trials.