Use of tyrosine kinase inhibitors during pregnancy for oncogenic-driven advanced non-small cell lung carcinoma

Anne-Sophie Boudy; Noémie Grausz; Lise Selleret; Joseph Gligorov; Isabelle Thomassin-Naggara; Cyril Touboul; Emile Daraï; Jacques Cadranel

doi:10.1016/j.lungcan.2021.09.001

Use of tyrosine kinase inhibitors during pregnancy for oncogenic-driven advanced non-small cell lung carcinoma

Lung Cancer. 2021 Nov:161:68-75. doi: 10.1016/j.lungcan.2021.09.001. Epub 2021 Sep 11.

Authors

Anne-Sophie Boudy¹, Noémie Grausz², Lise Selleret³, Joseph Gligorov⁴, Isabelle Thomassin-Naggara⁵, Cyril Touboul⁶, Emile Daraï⁶, Jacques Cadranel⁷

Affiliations

¹ Department of Gynaecology and Obstetrics, Tenon Hospital, Sorbonne University, Assistance Publique des Hôpitaux de Paris (AP-HP), France; Cancer Associé à La Grossesse (CALG), French National CALG Network, Sorbonne University, France. Electronic address: annesophie.boudy@aphp.fr.
² Department of Gynaecology and Obstetrics, Tenon Hospital, Sorbonne University, Assistance Publique des Hôpitaux de Paris (AP-HP), France.
³ Department of Gynaecology and Obstetrics, Tenon Hospital, Sorbonne University, Assistance Publique des Hôpitaux de Paris (AP-HP), France; Cancer Associé à La Grossesse (CALG), French National CALG Network, Sorbonne University, France.
⁴ Cancer Associé à La Grossesse (CALG), French National CALG Network, Sorbonne University, France; APHP Tenon, INSERM U938, IUC-UPMC, Sorbonne University, Paris, France.
⁵ Cancer Associé à La Grossesse (CALG), French National CALG Network, Sorbonne University, France; APHP Tenon, INSERM U938, IUC-UPMC, Sorbonne University, Paris, France; Department of Radiology, Tenon Hospital, Sorbonne University, Assistance Publique des Hôpitaux de Paris (AP-HP), France.
⁶ Department of Gynaecology and Obstetrics, Tenon Hospital, Sorbonne University, Assistance Publique des Hôpitaux de Paris (AP-HP), France; Cancer Associé à La Grossesse (CALG), French National CALG Network, Sorbonne University, France; APHP Tenon, INSERM U938, IUC-UPMC, Sorbonne University, Paris, France.
⁷ Department of Pulmonology and Thoracic Oncology, Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Tenon and GRC 04 Theranoscan, Sorbonne Université, Paris 75970, France. Electronic address: jacques.cadranel@aphp.fr.

PMID: 34543940
DOI: 10.1016/j.lungcan.2021.09.001

Abstract

Introduction: Lung cancer associated with pregnancy is rare but on the increase. The use of tyrosine kinase inhibitor (TKI) therapy for advanced oncogenic-driven non-small cell lung carcinoma (NSCLC) has improved overall survival. Oncological and obstetric outcomes of patients diagnosed with NSCLC and treated by TKIs during pregnancy have been poorly evaluated.

Methods: Three cases of NSCLC treated by TKIs during pregnancy were collected from the prospective database of the Cancer Associé à La Grossesse (CALG) network (France) in addition to eight cases identified by a systematic review performed between 2000 and 2021.

Results: Among the eleven reported patients, six received an EGFR- and five an ALK-TKI. All patients were young nonsmokers and four had brain metastases at diagnosis. TKI treatment was initiated during the first trimester for three patients. Premature delivery was induced in 10/11 patients. Anamnios occurred in one patient treated by osimertinib and trastuzumab. Five newborns were hypotrophic. No newborn malformations were observed. Diffusion of the TKIs, confirmed by blood cord sampling, represented about 1/3 (EGFR-TKI) and 1/8 (ALK-TKI) of the maternal concentration. No developmental abnormalities were observed in the children (follow-up 30 months). The anti-tumor efficacy and tolerance of TKIs, when reported, appears similar to that described in the general population.

Conclusions: Our results support the rationale for using TKIs during pregnancy, both in terms of maternal NSCLC disease control and the relatively mild effects on the fetus. Our data will serve to better inform patients about the risks associated with TKIs used during pregnancy, contributing to shared decision making.

Keywords: ALK and EGFR Tyrosine kinase inhibitors; Cancer associated with pregnancy; Lung cancer; Targeted therapy; Teratogenicity.

Publication types

Systematic Review

MeSH terms

Carcinoma, Non-Small-Cell Lung* / drug therapy
ErbB Receptors / genetics
Female
Humans
Infant, Newborn
Lung Neoplasms* / drug therapy
Molecular Targeted Therapy
Mutation
Pregnancy
Protein Kinase Inhibitors / adverse effects

Substances

Protein Kinase Inhibitors
ErbB Receptors