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| Ref Type | Journal Article | ||||||||||||
| PMID | (40441332) | ||||||||||||
| Authors | Yao Z, Tang M, Jin Y, Ruan J, Hu Y, Xie H, Wang Z, Fu L, Huang X, Zhou X, Zou B, Liu G, Zheng L, Lu Y | ||||||||||||
| Title | Brief Report: Successful Pregnancy and Healthy Baby Outcome in a TKI-refractory ALK+ NSCLC Patient with CNS Metastasis Treated with Lorlatinib with Maternal-fetal Pharmacokinetics and Child Milestone Development Correlations. | ||||||||||||
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| Abstract Text | Lorlatinib is the preferred first-line treatment for advanced anaplastic lymphoma kinase (ALK)+ non-small cell lung cancer (NSCLC) based on the 5-year CROWN update. However, the effects of lorlatinib on the fetus and neonate remain unknown.We report the first case of a patient with metastatic ALK-positive NSCLC who became pregnant during treatment with lorlatinib. A literature review was performed to identify all previously reported pregnancies of ALK-positive NSCLC. The collection, determination, and analysis of lorlatinib pharmacokinetics and mass spectroscopy imaging of lorlatinib are both performed.A 33-year-old pregnant woman, with a 7-year history of ALK-positive mNSCLC, was admitted to the hospital with brain metastases recurrence at 20 weeks of gestation. She self-discontinued lorlatinib at 4 weeks of gestation after long-term disease control on a reduced dose. According to patient's preference, low dose lorlatinib was re-introduced at 20 weeks, with successful tumor control and normal fetal growth. At 20-month follow-up post-partum, the mother maintained intracranial and systemic remission and no congenital abnormalities were observed in the baby. Pharmacokinetic analyses and mass spectroscopy imaging peri-delivery confirmed placental transfer of lorlatinib.The case highlights both the potential safety and safety concerns with the use of lorlatinib during pregnancy, along with the unique nature of CNS-dominant ALK-positive NSCLC, the potential clinical utility of dose-reduced lorlatinib. | ||||||||||||
| Molecular Profile | Treatment Approach |
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| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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| ALK rearrange | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, restarting Lorbrena (lorlatinib) at 20 weeks of gestation resulted in a near complete response in the brain metastases within 1 month in a pregnant patient with metastatic lung adenocarcinoma harboring an ALK rearrangement, with normal fetal growth and delivery of a healthy baby, the patient remained in remission and the child developed normaly except a slight mental development delay at 20 months post birth (PMID: 40441332). | 40441332 |