Fertility preservation and management of pregnancy in melanoma patients requiring systemic therapy.

Melanoma is one of the most common cancers in adolescents and adults at fertile age, especially in women. With novel and more effective systemic therapies that began to profoundly change the dismal outcome of melanoma by prolonging overall survival, the wish for fertility preservation or even parenthood has to be considered for a growing portion of melanoma patients-from the patients' as well as from the physicians' perspective. The dual blockade of the mitogen-activated protein kinase pathway by B-Raf proto-oncogene serine/threonine kinase and mitogen-activated protein kinase inhibitors and the immune checkpoint inhibition by anti-programmed cell death protein 1 and anti-cytotoxic T-lymphocyte-associated protein-4 monoclonal antibodies constitute the current standard systemic approaches to combat locally advanced or metastatic melanoma. Here, the preclinical data and clinical evidence of these systemic therapies are reviewed in terms of their potential gonadotoxicity, teratogenicity, embryotoxicity and fetotoxicity. Recommendations for routine fertility and contraception counseling of melanoma patients at fertile age are provided in line with interdisciplinary recommendations for the diagnostic work-up of these patients and for fertility-protective measures. Differentiated recommendations for the systemic therapy in both the adjuvant and the advanced, metastatic treatment situation are given. In addition, the challenges of pregnancy during systemic melanoma therapy are discussed.

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Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure The authors declare the following potential conflicts of interest: JCH reports personal fees and non-financial support from Novartis, during the conduct of the study; grants from BMS; and personal fees from Almirall, BMS, MSD, Roche, Novartis, Pfizer, Pierre Fabre, Sanofi and Sun Pharma, outside the submitted work. EL reports personal fees and non-financial support from Novartis, during the conduct of the study, and personal fees and other from Amgen, BMS, medac, MSD, Novartis, Pierre Fabre, Sanofi and Sun Pharma, outside the submitted work. JPA, HMB, JB, HHK, JL, FN and AS report personal fees and non-financial support from Novartis during the conduct of the study. LS reports personal fees and non-financial support from Novartis, during the conduct of the study; grants and personal fees from BMS; and personal fees and non-financial support from Pierre Fabre, BMS and MSD, outside the submitted work. KMT reports personal fees and non-financial support from Novartis, during the conduct of the study, and personal fees from Bristol-Myers Squibb, Galderma, Leo Pharma, MSD, Novartis, Pierre Fabre, Roche, Sanofi and Sun Pharma, outside the submitted work. LK reports personal fees and non-financial support from Novartis, during the conduct of the study, and personal fees from AbbVie, Actavis, AstraZeneca, Exeltis, Ferring Pharmaceuticals A/S, Gedeon Richter, Dr Kade/Besins, Pantarhei, Mithra Pharmaceuticals SA, Palleos Pharma GmbH, Roche and Shionogi, outside the submitted work. CB reports personal fees and non-financial support from Novartis, during the conduct of the study; personal fees and non-financial support from Bristol-Myers Squibb; and personal fees from Immunocore, Merck, MSD, Novartis, Pierre Fabre, Regeneron, Roche and Sanofi, outside the submitted work.