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

Sameh Daher*, Alona Zer, Roi Tschernichovsky, Rinat Yacobi, Iris Barshack, Shani Tsabari, Yakir Rottenberg, Aviad Zick, Teodor Gottfried, Anastasiya Lobachov, Edith M. Marom, Damien Urban, Akram Saad, Hadas Gantz-Sorotsky, Amir Onn, Jair Bar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: 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. Materials and Methods: 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). Results: 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). Conclusion: In a small minority of NSCLC patients with PIK3CA mutation there are no additional AGA. PIK3CA mutations may be actionable in these cases.

Original languageEnglish
Pages (from-to)229-236
Number of pages8
JournalLung Cancer
Volume178
DOIs
StatePublished - Apr 2023

Keywords

  • Actionable genomic alterations
  • Non-small cell lung cancer
  • PIK3CA
  • Targeted therapy

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