Immune‐related adverse events are associated with improved response, progression‐free survival, and overall survival for patients with head and neck cancer receiving immune checkpoint inhibitors

Abstract

BACKGROUND:The authors hypothesized that patients developing immune-related adverse events (irAEs) while receiving immune checkpoint inhibition (ICI) for recurrent/metastatic head and neck cancer (HNC) would have improved oncologic outcomes. METHODS: Patients with recurrent/metastatic HNC received ICI at 2 centers. Univariate and multivariate logistic regression, Kaplan-Meier methods, and Cox proportional hazards regression were used to associate the irAE status with the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in cohort 1 (n = 108). These outcomes were also analyzed in an independent cohort of patients receiving ICI (cohort 2; 47 evaluable for irAEs). RESULTS: The median follow-up was 8.4 months for patients treated in cohort 1. Sixty irAEs occurred in 49 of 108 patients with 5 grade 3 or higher irAEs (10.2%). ORR was higher for irAE+ patients (30.6%) in comparison with irAE− patients (12.3%; P = .02). The median PFS was 6.9 months for irAE+ patients and 2.1 months for irAE− patients (P = .0004), and the median OS was 12.5 and 6.8 months, respectively (P = .007). Experiencing 1 or more irAEs remained associated with ORR (P = .03), PFS (P = .003), and OS (P = .004) in multivariate analyses. The association between development of irAEs and prolonged OS persisted in a 22-week landmark analysis (P = .049). The association between development of irAEs and favorable outcomes was verified in cohort 2. CONCLUSIONS: The development of irAEs was strongly associated with an ICI benefit, including overall response, PFS, and OS, in 2 separate cohorts of patients with recurrent/metastatic HNC.

Reply to “Guarantee‐time bias in studies on the relationship between immune‐related adverse events and antitumor activity”

“…Although further testing in larger series will potentially verify or refute the concerns raised by Cheung et al, we believe that there is a strong biological rationale as well as sufficient data to support the validity of immune‐related adverse events (irAEs) as biomarkers of immunotherapy efficacy as signaled in our retrospective series 1 . A few considerations that we would like to highlight include the following: Cheung et al appropriately make a comparison with acneiform rash for epidermal growth factor receptor (EGFR) inhibitors and point out that the early appearance of rash largely abrogates the risk for guarantee‐time bias.…”

Immune Checkpoint Inhibitor-Induced Myositis/Myocarditis with Myasthenia Gravis-like Misleading Presentation: A Case Series in Intensive Care Unit

“…Although potentially life-threatening, irAEs have been significantly associated with an ICI benefit regarding overall response rate, progression-free survival, and overall survival in patients with recurrent/metastatic solid cancer [ 46 , 47 , 48 ]. Our first case illustrates this hypothesis.…”

Contribution of the Skin–Gut Axis to Immune-Related Adverse Events with Multi-System Involvement

“…Various organ systems can be affected by irAEs, though the skin, gastrointestinal, endocrine, and pulmonary systems are affected most often. It is unclear why some patients are more affected by irAEs than others, although some evidence suggests that irAEs may be associated with increased ICB efficacy and patient survival [ 5 , 6 , 7 ].…”