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    Adjuvant immunotherapy: the sting in the tail

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    Authors
    Higham, Claire E
    Chatzimavridou-Grigoriadou, Viktoria
    Fitzgerald, CT
    Trainer, Peter J
    Eggermont, AMM
    Lorigan, Paul C
    Affiliation
    Department of Endocrinology, Christie Hospital NHS Foundation Trust, Manchester
    Issue Date
    2020
    
    Metadata
    Show full item record
    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.
    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.
    Journal
    European Journal of Cancer
    URI
    http://hdl.handle.net/10541/623123
    DOI
    10.1016/j.ejca.2020.03.016
    PubMed ID
    32388064
    Additional Links
    https://dx.doi.org/10.1016/j.ejca.2020.03.016
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ejca.2020.03.016
    Scopus Count
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