A pregnant patient with ALK‑positive non‑small cell lung cancer treated with alectinib: A case report and review of the literature

Abstract

Oncogenic rearrangements in the anaplastic lymphoma kinase (ALK) gene account for 5% of non-small cell lung cancer (NSCLC) cases. ALK inhibitors have markedly improved the outcome of metastatic ALK-positive NSCLC (ALK + mNSCLC) by increasing long-term overall survival. Although a diagnosis of NSCLC during pregnancy or the peripartum period is rare, ALK + NSCLC accounts for 38% of NSCLC cases in women of childbearing age (18-45 years old). The younger age and prolonged survival of patients with ALK + mNSCLC bring new challenges for lung cancer and obstetrics research, and raises questions related to pregnancy and family planning. The present study described normal fetal development and no obstetric complications in a patient infected with HIV diagnosed with ALK + mNSCLC, who became pregnant during treatment with alectinib, a third-generation ALK inhibitor.

Treating anaplastic lymphoma kinase (ALK) fusion-driven metastatic non-small cell lung cancer (NSCLC) with alectinib through pregnancy

“…In our case, C-section was prompted by term premature rupture of membranes, while the case reported by Scarfone et al 11 was complicated by fetal acute respiratory distress syndrome. The other four cases had shorter in utero drug exposure—less than 4 weeks in four cases13–15 and 32 weeks in De Smedt et al 12 where alectinib was stopped about 5 weeks prior to delivery after weighing disease stability against unknown effects on fetal development. Reassuringly, circulating TKI concentrations in cord blood and amniotic fluid has been reported to be <9% of that in maternal blood 11 13.…”

“…In table 1, we compare our case against those six published case reports 11–15. Only one of these prior cases had a comparably lengthy in utero exposure to alectinib of about 36 weeks.…”

“…The first published case from Italy involved a similar duration of in utero exposure of alectinib (35 weeks and 5 days) 11. Another case from Belgium reported a shorter 32 weeks of in utero exposure of alectinib 12. A third case from France involved a very short duration of in utero exposure of alectinib (22 days only) 13.…”

“…Boudy et al 13 also identified three additional cases where patients received short courses (3–5 weeks) of first-generation ALK inhibitors (crizotinib or ceritinib) for ALK-rearranged metastatic NSCLC during pregnancy 13–15. In contrast, at least eight published case reports identified by Boudy et al 13 involved expediting delivery, sometimes with induced premature delivery, to allow initiation of indicated TKI therapy in the postpartum setting 12…”

Multifaceted Roles of ALK Family Receptors and Augmentor Ligands in Health and Disease: A Comprehensive Review

“…In contrast, a CNS-penetrable ALK inhibitor, Lorlatinib, has shown severe teratogenicity in mice, leading to malformations and abortion (Pfizer report). However, in humans, two clinical cases of pregnant patients treated with alectinib resulted in normal childbirth and development [114,115]. During embryological development, ALK is present throughout the CNS, including in specific regions of the brain such as the thalamus, mid-brain, olfactory bulb, and ganglia [98,110].…”