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Adjuvant immunotherapy: the sting in the tail
Higham, Claire E Chatzimavridou-Grigoriadou, Viktoria Fitzgerald, CT Trainer, Peter J Eggermont, AMM Lorigan, Paul C
Higham, Claire E
Chatzimavridou-Grigoriadou, Viktoria
Fitzgerald, CT
Trainer, Peter J
Eggermont, AMM
Lorigan, Paul C
Citations
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Abstract
Adjuvant therapy with PD-1 inhibitors for resected Stage III/IV melanoma reduces the risk of recurrence by 40-50% and is now a standard of care. Immune-related adverse events occurred in approximately 37% of patients in the pivotal trials, 10-15% were severe (grade III-IV). Endocrine toxicities were common and mostly irreversible. Thyroid toxicity occurred in 15-20% of patients, hypophysitis (2.2%), insulin-dependent diabetes mellitus (1%) and adrenalitis (1%). Revision of the American Joint Committee on Cancer staging system (version 8) has resulted in a significant improvement in prognosis for patients with Stage III disease. As a result, clinicians may now offer adjuvant immunotherapy to patients with a lower risk of recurrence than those in the pivotal trials. There is a need to balance the relatively small reduction of absolute risk of recurrence against the risk and impact of toxicity. Five-ten percent of biochemically euthyroid patients on levothyroxine report symptoms of depression. Hypogonadism can result from toxicity to the hypothalamic-pituitary axis, and can lead to sexual dysfunction and subfertility. Secondary hypogonadism can be treated by the administration of Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH) which induce spermatogenesis/ovulation in a functioning gonad but is not always successful. Insulin-dependent diabetes mellitus often presents with rapid onset of hyperglycemia and potentially life-threatening diabetic ketoacidosis. Long-term adverse outcomes are likely to mimic Type 1 DM with a 6-fold increase in cardiovascular disease related mortality and 3-fold in all-cause mortality. These survivorship issues are relevant to all melanoma patients but are particularly pertinent where the absolute benefit is modest.
Keywords: Adjuvant immunotherapy; Endocrine toxicity; Fertility; Late effects; Melanoma.
Authors
Higham, Claire E
Chatzimavridou-Grigoriadou, Viktoria
Fitzgerald, CT
Trainer, Peter J
Eggermont, AMM
Lorigan, Paul C
Chatzimavridou-Grigoriadou, Viktoria
Fitzgerald, CT
Trainer, Peter J
Eggermont, AMM
Lorigan, Paul C
Description
Date
2020
Publisher
Collections
Keywords
Type
Article
Citation
Higham CE, Chatzimavridou-Grigoriadou V, Fitzgerald CT, Trainer PJ, Eggermont AMM, Lorigan P. Adjuvant immunotherapy: the sting in the tail. Eur J Cancer. 2020;132:207-10.