Associations between patient and disease characteristics and severe adverse events during immune checkpoint inhibitor treatment: An observational study

• Published in: European journal of cancer (1990) 2022-10, Vol.174, p.113-120
• Main Authors: Basak, Edwin A., Vermeer, Niels S., de Joode, Karlijn, Hurkmans, Daan P., Velthuis, Dorian E.M., Oomen-de Hoop, Esther, Schreurs, Marco W.J., Bins, Sander, Koolen, Stijn L.W., Debets, Reno, van der Veldt, Astrid A.M., Aerts, Joachim G.J.V., Joosse, Arjen, Mathijssen, Ron H.J.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Anti-CTLA-4; Anti-PD-1; Cancer; Carcinoma, Non-Small-Cell Lung; Cohort Studies; CTLA-4 protein; Histology; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - adverse effects; Lung cancer; Lung Neoplasms; Melanoma; Melanoma - drug therapy; Non-small cell lung carcinoma; NSCLC; Observational studies; Patients; PD-1 protein; Prediction models; Regression models; Retrospective Studies; Severe immune-related adverse events; Squamous cell carcinoma; Subgroups; Tumors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2022.07.015

With increasing use of immune checkpoint inhibitors (ICIs) more patients will develop severe and potentially life-threatening immune-related adverse events (irAEs). So far, predictive models for the occurrence of grade ≥3 irAEs are lacking. Therefore, we analysed associations between patient and disease characteristics, and the occurrence of grade ≥3 irAEs. Patients with cancer who were treated with anti-PD-1 (+/−anti-CTLA-4) between July 2015 and February 2020, and who were prospectively included in the MULTOMAB-trial, were eligible for this cohort study. Time to and occurrence of grade ≥3 irAEs according to CTCAE v5.0 were retrospectively registered. The associations between patient and disease characteristics and irAE occurrence were analysed using the competing risk cox-regression model of Fine and Gray. Analyses were performed separately in patients treated with monotherapy (anti-PD-1) and combination therapy (anti-PD-1 + anti-CTLA-4). Subgroup analyses were performed in tumour types with the highest number of patients; melanoma and NSCLC. Out of 641 patients, 106 patients (17%) experienced grade ≥3 irAEs. None of the analysed factors were associated with grade ≥3 irAE occurrence in the monotherapy (n = 550) or the combination therapy (n = 91) groups, nor in the subgroup analyses. Of interest, none of the patients with NSCLC with a WHO performance status of 0 (n = 34) experienced grade ≥3 irAEs. Most common NSCLC histology types were adenocarcinoma (n = 99/55%) and squamous cell carcinoma (n = 39/22%). This study shows that patient and disease characteristics are not able to predict the occurrence of serious AEs in patients treated with ICIs. •12% of patients receiving anti-PD-1 monotherapy experienced grade ≥3 toxicities.•44% of patients receiving anti-PD-1 + CTLA-4 therapy experienced grade ≥3 toxicities.•No clinical factor was associated with toxicities during anti-PD-1 (+CTLA4) therapy.•This was found across tumour types, as well as in melanoma and NSCLC patients.