Checkpoint inhibitors, fertility, pregnancy, and sexual life: a systematic review

Abstract

Immune checkpoint inhibitors (i.e. anti-PD1, anti-PDL1, and anti-CTLA4) have revolutionized the therapeutic approach of several cancer types. In a subset of metastatic patients, the duration of the response is so long that a cure might be hypothesized, and a treatment discontinuation strategy could be proposed. Considering that long-term efficacy, some patients could also plan to have a child. Moreover, immunotherapy is moving to the early setting in several diseases including melanoma and breast cancer that are common cancers in young patients. However, there is a paucity of data about their potential detrimental effect on fertility, pregnancy, or sexuality. Herein, we conducted a systematic review with the aim to comprehensively collect the available evidence about fertility, pregnancy, and sexual adverse effects of checkpoint inhibitors in order to help clinicians in daily practice and trialists to develop future studies.

Uncomplicated pregnancy and delivery under ongoing nivolumab therapy for metastatic melanoma

“…Although ICI does not appear to induce teratogenic effects, the use of immunotherapy, nevertheless, may present huge challenges for pregnancy because of activated immune responses may result in miscarriages, restricted fetal growth, or cause of immune-related adverse events (irAE) in the fetus or mother [1][2][3]. Sporadic clinical evidence is available in the form of case reports [4,5], describing both favorable and unfavorable outcomes of ICI as well as targeted therapy in pregnant melanoma patients.…”

“…The first described and most profound predictor of survival is monosomy 3, which can be partial or complete. Others include 1p loss or gain, 6p loss or gain, 6q loss or gain, 8p loss or gain and 8q loss or gain [2]. Whole-genome doubling (WGD) can occur in uveal melanoma, which could account for the tetrasomy found in this case [3].…”

“…Several articles recently addressed the issues linked to female cancer patients treated with immune checkpoint inhibitors (ICIs) under pregnancy [1–3]. Here, we reported a young pregnant female with metastatic melanoma of the brain who experienced an uncomplicated pregnancy and birth of a healthy child under ongoing nivolumab therapy.…”

Update on Pregnancy Following Breast Cancer Diagnosis and Treatment

“…These adverse effects may also be of concern for reproductive choices in young women because of their potential impact on the likelihood of subsequent conception and pregnancy complications. 52,53 While waiting for some evidence to help clinical practice in this regard, patients should be advised to avoid pregnancy during immunotherapy, using a contraceptive method for at least 4 months after termination of pembrolizumab and 5 months for atezolizumab. 52 Among emerging new treatments in the early breast cancer setting, olaparib should be mentioned for BRCA carriers.…”

“…52,53 While waiting for some evidence to help clinical practice in this regard, patients should be advised to avoid pregnancy during immunotherapy, using a contraceptive method for at least 4 months after termination of pembrolizumab and 5 months for atezolizumab. 52 Among emerging new treatments in the early breast cancer setting, olaparib should be mentioned for BRCA carriers. Its use is contraindicated during and while attempting pregnancy; in particular, according to the OlympiA study protocol, fertile patients had to agree to the use of 2 highly effective forms of contraception in combination throughout the period of study treatment administration and for at least 1 month after last dose of study drug (ClinicalTrials.gov: NCT02032823).…”