We thank Harrilal Khan et al for their insightful paper, which provides objective data showing that pregnant individuals remain largely excluded from clinical trials despite recommendations for their inclusion. We focus here on their worrying results in the oncology field. With the rising incidence of cancer during pregnancy, the treatment of pregnant patients with cancer is becoming an increasing concern. Harrilal Khan et al showed that the number of clinical trials in oncology has almost doubled between the 2 study periods (2015–2019 and 2019–2023), and yet two-thirds of them still exclude pregnant individuals. Because of this lack of data, emerging drugs, such as targeted therapies or immunotherapies, are contra-indicated in pregnancy.
Patients and physicians are subsequently left with the following limited therapeutic options for cancer treatment:
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Delaying specific therapies until after pregnancy, which might alter prognosis;
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Termination of pregnancy in case of highly aggressive cancers diagnosed during the first or early second trimester;
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Or preterm induction of labor in the early third trimester to start treatment as soon as possible, leading to possible iatrogenic neonatal consequences.
As an illustration, in our prenatal diagnosis center, 4 terminations of pregnancy have been performed in the past 6 months for individuals who needed pembrolizumab while pregnant, bringing into question the application of the principle primum non nocere .
Another way of obtaining data on emerging drugs in human pregnancy is to perform preclinical studies on human placenta. The transfer of drugs to the fetal circulation can be assessed ex vivo using the perfused cotyledon technique or in vitro via transwells or the placenta-on-chips technology. The effects of drugs on placental functions are assessed in vitro by exposing cells from immortalized cell lines or primary culture of human cytotrophoblasts from third-trimester placentas. Cytotoxicity and the ability to differentiate after drug exposure can be tested. Such studies do not, however, provide data on the possible teratogenicity, and systemic cancer drugs should not be prescribed during embryogenesis. But for the second and third trimesters, comparative preclinical studies help clinicians chose the most appropriate treatment option on an individual level with the help from the international Advisory Board on Cancer in Pregnancy.
Preclinical human placental studies are often conducted by researchers from public institutions who receive little to no funding from the industry. The price of emerging drugs thus greatly limits the possibilities for research. If no research is funded and published on the subject, individuals and physicians will have to wait decades for pharmacovigilance data on accidental exposures to these drugs. Meanwhile, pregnant individuals will not have access to the appropriate treatment, leading to the current critical issue.
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