Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens
- Study type
- Meta-analysis
- Design
- Systematic review and meta-analysis of randomised trials, using log-odds random effects models
- Sample size
- 7551 patients in 38 randomised trials
- Source
- JAMA Oncol · 2018
In plain words
Immunotherapy medicines (immune checkpoint inhibitors) sometimes affect the body's hormone-making glands, such as the thyroid and pituitary. This study combined the results of 38 trials with 7551 patients and showed that the risk of thyroid and pituitary problems is higher in people who receive two types of immunotherapy at the same time (PD-1 plus CTLA-4). If you are having immunotherapy, your doctor should follow up symptoms and gland-related tests, because late diagnosis of these side effects can be dangerous.
Key results
Treatment arms and regimens
Monotherapy with a PD-1 (programmed cell death protein 1) inhibitor. Dose details in the full text.
Monotherapy with a CTLA-4 (cytotoxic T-lymphocyte-associated protein-4) inhibitor, including ipilimumab. Dose details in the full text.
Monotherapy with a PD-L1 (programmed cell death 1 ligand 1) inhibitor. Dose details in the full text.
Combination therapy with a PD-1 inhibitor plus a CTLA-4 inhibitor. Dose details in the full text.
Source of the regimen details: Abstract of the paper (drug doses not given in the abstract; dose details in the full text)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with advanced solid tumours treated in 38 randomised trials with one of the US Food and Drug Administration (FDA)-approved immune checkpoint inhibitors (ICIs), including ipilimumab, nivolumab, pembrolizumab and atezolizumab (7551 eligible patients in total). PubMed was searched up to 18 July 2016.
Endpoints
Primary outcomes: incidence of hypothyroidism, hyperthyroidism, hypophysitis, primary adrenal insufficiency and insulin-deficient diabetes, all of any grade.
Safety and side effects
The study itself focuses on endocrine adverse events. The incidence of hypothyroidism and hyperthyroidism was highest in patients receiving combination therapy. For primary adrenal insufficiency and insulin-deficient diabetes, no statistical inference was made because of the small number of events. Exact incidence percentages are not reported in the abstract.
Clinical significance and place in guidelines
This meta-analysis provides more precise data on the incidence of endocrine disorders with different ICI regimens and shows that combination therapy is associated with a higher risk of thyroid dysfunction and hypophysitis. These findings emphasise the importance of clinical awareness and monitoring for endocrine disorders in patients receiving immunotherapy, particularly combination therapy. Detailed monitoring and management recommendations should be aligned with current authoritative clinical guidelines, as the abstract gives no specific practical recommendation.
Limitations
Because of the small number of events, statistical inference was not possible for primary adrenal insufficiency and insulin-deficient diabetes. The literature search extended to 18 July 2016 and does not include later data. Other limitations should be checked in the full text.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.