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

• DOI: 10.1016/j.lungcan.2023.02.023
• Publication Date: 2023-03-02T16:34:30Z
• Authors: 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
• Keywords: Male; Lung Neoplasms; Class I Phosphatidylinositol 3-Kinases; Carcinoma, Non-Small-Cell Lung; Catalytic Domain; Mutation; Carcinoma, Squamous Cell; Humans; Female; Adenocarcinoma; 3. Good health; Aged

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.