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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
[Fertility, teratogenicity, and contraception during therapy with BRAF/MEK inhibitors]
Elisabeth Livingstone1, Carola Berking2,3
1Klinik für Dermatologie, Allergologie und Venerologie, Universitätsmedizin Essen, Hufelandstr. 55, 45122, Essen, Deutschland. elisabeth.livingstone@uk-essen.de.
Background:
Targeted mutation-based therapy with BRAF and MEK inhibitors has become an integral part of systemic therapy for metastatic melanoma in the advanced setting and for the adjuvant therapy of melanoma in stage III after complete resection. Due to the increased chances of survival and early use in the adjuvant situation, fertility preservation as well as aspects of teratogenicity and pregnancy are increasingly relevant in patients who are often still young.
Objectives:
To communicate the published and study-based information on fertility preservation, teratogenicity and pregnancy under therapy with BRAF and MEK inhibitors.
Materials And Methods:
Summaries of product characteristics as well as studies and case reports on BRAF and MEK inhibitors published in PubMed were used as sources of information.
Results:
There are no specific preclinical studies or experience in humans on fertility, teratogenicity, and contraception with targeted therapy. Recommendations can only be derived from toxicity studies and individual case reports.
Conclusions:
Patients should be offered counseling on the options for fertility-protective measures before starting targeted therapy. Due to unclear teratogenicity, adjuvant melanoma therapy with dabrafenib and trametinib should not be initiated in pregnant patients. In the advanced metastatic situation, BRAF and MEK inhibitors should only be given after extensive interdisciplinary education and counselling of the pregnant patient and her partner. Patients should be informed about the need for adequate contraception during targeted therapy.
Insights
Targeted therapy for melanoma using BRAF and MEK inhibitors requires careful patient counseling regarding fertility preservation and potential risks during pregnancy. Limited data necessitates thorough education on contraception and teratogenicity before and during treatment.
Area of Science:
- Oncology
- Pharmacology
- Reproductive Medicine
Context:
- BRAF and MEK inhibitors are standard treatments for advanced and adjuvant melanoma.
- Young patients undergoing treatment raise concerns about fertility and pregnancy.
Purpose:
- To review available information on fertility preservation, teratogenicity, and pregnancy in patients treated with BRAF and MEK inhibitors.
- To guide clinical practice regarding reproductive health in melanoma patients receiving targeted therapy.
Summary:
- Preclinical and human data on fertility, teratogenicity, and contraception with targeted therapy are scarce.
- Recommendations are based on toxicity studies and individual case reports.
Impact:
- Patients must receive counseling on fertility preservation before initiating targeted therapy.
- Adjuvant therapy with dabrafenib and trametinib is contraindicated in pregnant patients due to unclear teratogenicity.
- Pregnant patients with metastatic melanoma require extensive interdisciplinary counseling and must use adequate contraception during treatment.
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