Rapid and durable response to fifth-line lorlatinib plus olaparib in an ALK -rearranged, BRCA2-mutated metastatic lung adenocarcinoma patient with critical tracheal stenosis: a case report.
Adenocarcinoma of Lung
/ drug therapy
Adult
Aminopyridines
Anaplastic Lymphoma Kinase
/ genetics
BRCA2 Protein
/ genetics
Carcinoma, Non-Small-Cell Lung
/ drug therapy
ErbB Receptors
Female
Humans
Lactams
Lactams, Macrocyclic
/ therapeutic use
Lung Neoplasms
/ drug therapy
Phthalazines
Piperazines
Poly(ADP-ribose) Polymerase Inhibitors
/ therapeutic use
Protein Kinase Inhibitors
/ pharmacology
Pyrazoles
Receptor Protein-Tyrosine Kinases
/ genetics
Tracheal Stenosis
/ drug therapy
Journal
Anti-cancer drugs
ISSN: 1473-5741
Titre abrégé: Anticancer Drugs
Pays: England
ID NLM: 9100823
Informations de publication
Date de publication:
01 08 2022
01 08 2022
Historique:
pubmed:
25
3
2022
medline:
16
7
2022
entrez:
24
3
2022
Statut:
ppublish
Résumé
Treatment options for heavily treated anaplastic lymphona kinase (ALK )-positive nonsmall cell lung cancer (NSCLC) patients, who typically bear-resistant mechanisms to ALK tyrosine kinase inhibitors (TKIs), are usually limited to chemotherapy, which elicits limited clinical benefit and may incur severe toxicity. It is clinically relevant to explore other revenues for these patients. poly (ADP-ribose) polymerase (PARP) inhibitors, such as olaparib are currently approved to treat BReast CAncer gene 1/2 ( BRCA1/2 )-mutated patients in a few tumor types. There have been a trial and two case reports of an olaparib-containing regimen in treating epidermal growth factor receptor (EGFR)-positive or driver-negative NSCLC. We report a case of a 27-year-old female nonsmoker diagnosed with ALK -rearranged metastatic lung adenocarcinoma. She was treated with alectinib and acquired ALK p.I1171N and p.V1180L mutations. Germline BRCA2 p.F2801fs was also identified. After sequential lines of ceritinib and chemotherapy, lorlatinib was chosen as the fourth-line therapy and maintained control for 6 months. Shortly after progression, the patient was admitted to the ICU due to critically severe stenosis caused by a tracheal mass and soon relieved by embolization and stenting. Afterward lorlatinib plus olaparib was started and elicited a rapid response within 1 month. The progression-free survival was 6 months as of the latest follow-up, with the best response of partial response. To the best of our knowledge, this case is the first to provide clinical evidence of antitumor activity of olaparib plus ALK TKI in ALK -positive, g BRCA -mutated metastatic NSCLC. Together with previous reports in EGFR -positive or driver-negative patients, our finding warrants further studies on PARP inhibition in BRCA1/2 -mutated NSCLC.
Identifiants
pubmed: 35324529
doi: 10.1097/CAD.0000000000001303
pii: 00001813-202208000-00012
doi:
Substances chimiques
Aminopyridines
0
BRCA2 Protein
0
BRCA2 protein, human
0
Lactams
0
Lactams, Macrocyclic
0
Phthalazines
0
Piperazines
0
Poly(ADP-ribose) Polymerase Inhibitors
0
Protein Kinase Inhibitors
0
Pyrazoles
0
Anaplastic Lymphoma Kinase
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
lorlatinib
OSP71S83EU
olaparib
WOH1JD9AR8
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
696-700Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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