Adjuvant immunotherapy: the sting in the tail. (June 2020)

• Record Type: Journal Article
• Authors: Higham, Claire E.; Chatzimavridou-Grigoriadou, Viktoria; Fitzgerald, Cheryl T.; Trainer, Peter J.; Eggermont, Alexander M.M.; Lorigan, Paul
• Is Part Of: European journal of cancer. Volume 132(2020)
• Page Start: 207
• Page End: 210
• Publication Date: 2020-06
• Subjects: Adjuvant immunotherapy -- Melanoma -- Endocrine toxicity -- Fertility -- Late effects; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2020.03.016
• Languages: English
• ISSNs: 0959-8049

Abstract

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. Highlights: Adjuvant immunotherapy is approved for stage III patients, many of which have a low risk of recurrence. Immunotherapy induced endocrine toxicities are irreversible and can potentially reduce life expectancy in cured patients. There is no consensus on how to manage potential immunotherapy-induced infertility.