Driver mutation characteristics of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in advanced non-small cell lung cancer.


Journal

Lung cancer (Amsterdam, Netherlands)
ISSN: 1872-8332
Titre abrégé: Lung Cancer
Pays: Ireland
ID NLM: 8800805

Informations de publication

Date de publication:
04 2023
Historique:
received: 16 12 2022
revised: 22 02 2023
accepted: 27 02 2023
medline: 31 3 2023
pubmed: 11 3 2023
entrez: 10 3 2023
Statut: ppublish

Résumé

The identification and targeting of actionable genomic alterations (AGA) have revolutionized the treatment of cancer in general and mostly for non-small cell lung cancer (NSCLC). We investigated whether in NSCLC patients PIK3CA mutations are actionable. Chart review was performed of advanced NSCLC patients. PIK3CA mutated patients were analyzed as two groups: Group A: without any non-PIK3CA established AGA; Group B: with coexisting AGA. Group A was compared to a cohort of non-PIK3CA patients (group C), using t-test and chi-square. To evaluate the impact of PIK3CA mutation on outcome, we compared Group A survival to age/sex/histology matched cohort of non-PIK3CA mutated patients (group D) by Kaplan-Meier method. A patient with a PIK3CA mutation was treated with a PI3Ka-isoform selective inhibitor BYL719 (Alpelisib). Of a cohort of 1377 patients, 57 are PIK3CA mutated (4.1%). Group A: n-22, group B: n-35. Group A median age is 76 years, 16 (72.7%) men, 10 (45.5%) squamous, 4 (18.2%) never smokers. Two never-smoker female adenocarcinoma patients had solitary PIK3CA mutation. One of them was treated with a PI3Ka-isoform selective inhibitor BYL719 (Alpelisib), with rapid clinical and partial radiological improvement. Group B, compared with Group A, included younger patients (p = 0.030), more females (p = 0.028) and more adenocarcinoma cases (p < 0.001). Compared to group C, group A patients were older (p = 0.030) and had more squamous histology (p = 0.011). In a small minority of NSCLC patients with PIK3CA mutation there are no additional AGA. PIK3CA mutations may be actionable in these cases.

Identifiants

pubmed: 36898331
pii: S0169-5002(23)00084-3
doi: 10.1016/j.lungcan.2023.02.023
pii:
doi:

Substances chimiques

Alpelisib 08W5N2C97Q
Class I Phosphatidylinositol 3-Kinases EC 2.7.1.137
PIK3CA protein, human EC 2.7.1.137

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

229-236

Informations de copyright

Copyright © 2023. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Sameh Daher (S)

Thoracic Cancer Unit, Cancer Center, Sheba Medical Center, Tel HaShomer, Ramat Gan 52621, Israel. Electronic address: s_daher@rambam.health.gov.il.

Alona Zer (A)

Davidoff Cancer Center, Rabin Medical Center, Beilinson Campus, Petah Tikva 49100, Israel.

Roi Tschernichovsky (R)

Davidoff Cancer Center, Rabin Medical Center, Beilinson Campus, Petah Tikva 49100, Israel.

Rinat Yacobi (R)

Institute of Pathology, Sheba Medical Center, Tel HaShomer, Ramat Gan 52621, Israel.

Iris Barshack (I)

Institute of Pathology, Sheba Medical Center, Tel HaShomer, Ramat Gan 52621, Israel.

Shani Tsabari (S)

Department of Oncology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, 91120, Israel.

Yakir Rottenberg (Y)

Department of Oncology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, 91120, Israel.

Aviad Zick (A)

Department of Oncology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, 91120, Israel.

Teodor Gottfried (T)

Thoracic Cancer Unit, Cancer Center, Sheba Medical Center, Tel HaShomer, Ramat Gan 52621, Israel.

Anastasiya Lobachov (A)

Thoracic Cancer Unit, Cancer Center, Sheba Medical Center, Tel HaShomer, Ramat Gan 52621, Israel.

Edith M Marom (EM)

Radiology Department, Sheba Medical Center, Tel HaShomer, Ramat Gan 52621, Israel; Tel Aviv University School of Medicine, Tel Aviv 69978, Israel.

Damien Urban (D)

Thoracic Cancer Unit, Cancer Center, Sheba Medical Center, Tel HaShomer, Ramat Gan 52621, Israel; Tel Aviv University School of Medicine, Tel Aviv 69978, Israel.

Akram Saad (A)

Thoracic Cancer Unit, Cancer Center, Sheba Medical Center, Tel HaShomer, Ramat Gan 52621, Israel; Tel Aviv University School of Medicine, Tel Aviv 69978, Israel.

Hadas Gantz-Sorotsky (H)

Thoracic Cancer Unit, Cancer Center, Sheba Medical Center, Tel HaShomer, Ramat Gan 52621, Israel.

Amir Onn (A)

Thoracic Cancer Unit, Cancer Center, Sheba Medical Center, Tel HaShomer, Ramat Gan 52621, Israel.

Jair Bar (J)

Thoracic Cancer Unit, Cancer Center, Sheba Medical Center, Tel HaShomer, Ramat Gan 52621, Israel; Tel Aviv University School of Medicine, Tel Aviv 69978, Israel.

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Classifications MeSH