A comprehensive meta-analysis of endocrine immune-related adverse events of immune checkpoint inhibitors and outcomes in head and neck cancer and lung cancer.

Abstract

e14096 Background: Immune checkpoint inhibitors (ICPi) have emerged as an effective treatment for a variety of cancers. However, important immune-related adverse events (irAEs) can occur. The aim of this study was to determine the prevalence of endocrine irAEs in patients with head and neck cancer and lung cancer that have used a ICPi and outcomes. Methods: A systematic literature review was performed within PubMed and EMBASE databases. Search terms included “durvalumab”, “atezolizumab”, “nivolumab”, “pembrolizumab”, “ipilimumab”, “head & neck cancer”, “lung cancer”. Studies published before September 2018 were included. The search was limited to randomized controlled trials (RCTs) phase III written in English. Data were extracted about patient characteristics, interventions, overall survival (OS), progression free survival (PFS), and endocrine irAEs. A summary hazard ratio (HR) and 95% confidence interval were calculated using the software Comprehensive Meta-Analysis and a scatter plot was generated. Results: Twelve RCTs comprising 7060 patients were reviewed; 3815 used an ICPi (treatment arm). The mean follow-up time of 12.2 months ± 7.1 SD. The survival rate of the treatment arm was enhanced (HR, 0.75; 95% CI, 0.70-0.80), compared to the alternate arm. Similarly, the PFS of the treatment arm was improved (HR, 0.77; 95% CI, 0.72-0.81) but with a higher incidence of endocrine irAEs. The most common endocrine irAE reported was hypothyroidism;193 patients in the treatment arm vs. 29 in the alternate arm (p < 0.001); grade 3/4 AE was observed in 10 patients vs. 1 patient, respectively. Other endocrine irAEs were reported in 168 patients in the treatment arm vs. 26 patients in the alternate arm (p < 0.001); grade 3/4 AE was observed in 28 patients vs. 3 patients, respectively. A significant positive correlation between endocrine irAEs and OS was observed (p = 0.019). Conclusions: ICPi are a powerful tool in the treatment of cancer. The prevalence of endocrine irAEs in this meta-analysis was 9%. There is evidence of improved overall survival in patients who developed endocrine irAEs. Further studies are needed to correlate the development of irAEs and OS advantage.

Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors

“…A systematic literature review pooling 12 RCTs identified 3815 metastatic head & neck and lung cancer patients treated with ICIs (unspecified distribution of anti-PD-1 and anti-CTLA-4 antibodies) [54]. The primary aim of the analysis was to assess the prevalence of endocrine IRAEs and the association between endocrine IRAEs and patient outcomes.…”

Racial disparities in immune-related adverse events of immune checkpoint inhibitors and association with survival based on clinical and biochemical responses

“…Other studies reported similar outcomes in patients with NSCLC who had thyroid AE following treatment with immunotherapy[ 9 , 10 , 18 ]. A preliminary study from our group also addressed this issue with a systematic literature review and meta-analysis of patients with lung cancer and head and neck cancer on immune checkpoint inhibitor therapy across twelve randomized-controlled trials comprising of 7060 patients with 3815 patients using ICPi[ 19 ]. In that study, at a mean follow-up of 12.2 mo, the OS (hazard ratio: 0.75; 95% credibility interval: 0.70-0.80) and PFS (hazard ratio: 0.77; 95% credibility interval: 0.72-0.81) in the ICPi arm were significantly improved.…”

The Impact of Adverse Events on Health Care Resource Utilization, Costs, and Mortality Among Patients Treated with Immune Checkpoint Inhibitors

“…The site of the irAE may also have an impact on outcomes. In a meta‐analysis of head, neck, and lung cancer clinical trials, endocrine irAEs were associated with improved overall survival ( p = .019) [ 55 ], whereas in patients with melanoma dermatologic irAEs resulted in increased survival rates ( p < .001) [ 56 ]. In Ricciuti et al, dermatologic and hepatic‐gallbladder reactions did not result in improved overall survival, but pulmonary, endocrine, and gastrointestinal irAEs did in patients with stage IV NSCLC [ 57 ].…”