Adjuvant immunotherapy: the sting in the tail

Claire E. Higham, Viktoria Chatzimavridou-Grigoriadou, Cheryl T. Fitzgerald, Peter J. Trainer, Alexander M.M. Eggermont, Paul Lorigan

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

18 Citaten (Scopus)


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.

Originele taal-2Engels
Pagina's (van-tot)207-210
Aantal pagina's4
TijdschriftEuropean Journal of Cancer
StatusGepubliceerd - jun. 2020


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