How do ALK TKIs Affect Pregnancy?
Studies on ALK TKIs* and Pregnancy
In 2016, there was a study reported by Dr. Ibiayi et. al. (Dr. Shaw’s group) on patients who were pregnant or had just given birth to a child while diagnosed with NSCLC (non-small cell lung cancer) between 2009 and 2015. They identified 2422 women with lung cancer of whom 160 were of reproductive age. The majority of the 160 women within childbearing age diagnosed with NSCLC had some type of a genetic mutation such as EGFR, ALK, KRAS, or ROS1. Eight cases were diagnosed while pregnant or very close post-birth (peripartum). Six out of the eight identified were ALK-positive and the two remaining were EGFR-positive.
Two ALK patients who were diagnosed early in gestation elected to terminate their pregnancy. The remaining six continued to carry their pregnancies. Several complications did occur but these were not linked to lung cancer. None of the women were treated during pregnancy, however one did receive chemotherapy (carboplatin and paclitaxel) during her second and third trimester. In addition, this patient had gamma knife for her brain metastases during her second trimester.
The first line TKI, Crizotinib, was given to all ALK patients and the medium progression-free survival (PFS) was 16 weeks. Progression was mostly extracranial and 3 patients had intracranial progression. One patient had lung progression but no brain progression. At the time of publication, 5 out of the 6 ALK patients were still in therapy. The only patient who passed away died of leptomeningeal spread of her NSCLC after 2 years of treatment. Learn more about this study Here.
In 2018, a Japanese group reported a case where a pregnant patient had NSCLC and was ALK-positive. The patient was diagnosed 34 weeks into her pregnancy. She delivered the baby at 37 weeks via C-section and was treated with Alectinib postpartum. Learn more about this Here.
In 2019, a group in Isreal raised the question whether being on an ALK inhibitor is a contraindication for subsequent pregnancy via IVF. Learn more Here.
However, Pfizer indicates that use of their drugs Crizotinib (Xalkori) and Loratinib (Lorbrena) can cause fetal farm and does not recommend taking the medication while pregnant. Learn more Here and Here.
Alectinib maker, Genetech, also recommends that Alectinib is not used during pregnancy. Learn more Here.
Takeda, the maker of Brigatinib (Alunbrig) also recommends that Brigatinib should not be used during pregnancy. The recommendation is based on animal model results that indicated Brigatinib may cause fetal harm. Learn more Here.
Novartis, the maker of Ceritinib (Zykadia) indicated that there were skeletal anomalies in animal (rats and rabbits) if medication was given during organ development. Again, the medication is not recommended for use during pregnancy. Learn more Here.
All drug makers did recommend effective contraception during treatment and for several months after the last dose of a TKI.
*TKIs stand for Tyrosine Kinase Inhibitors and they are the type of targeted medicine that are recommended for Stage IV ALK Lung Cancer, according to NCCN guidelines. They include first generation drug Crizotinib, second generation drugs Certinib, Alectinib, Brigatinib (and Ensartinib, still in trials) and third generation drug Lorlatinib.