Abstract 1359P
Background
PIK3CA mutations are investigated as potential driver mutations in NSCLC. Efficacy of targeted therapy for this pathway is not clear. We examined if NSCLC patients with PI3KCA mutations have driver mutation characteristics.
Methods
Chart review was performed for advanced NSCLC patients treated at Israeli medical centres during 2015 – 2019, with available next generation sequencing (NGS) results. PIK3CA mutated patients were divided into two groups: Group A - without established driver mutation; Group B - with coexisting driver mutation. We compared several factors between the groups, using t-test and chi-square. We compared survival in Group A to a matched cohort of non-PI3KCA mutated patients (Group C) (ratio of 1:2, respectively), analysed by Kaplan-Meier method.
Results
A total of 948 patients were analysed, with a PIK3CA mutation identified in 35 patients (4%). Characteristics: median age 70 years, 21 (60%) men, 21 (60%) adenocarcinoma, 8 (24%) never smokers. There were 12 patients in group A and 23 in group B. Group A characteristics: median age 77 years, 9 (75%) men, 9 (75%) squamous, 2 (17%) never smoker. PDL1 expression (data missing for 1 patient): 3 (27%) negative, 4 (36.5%) 1-49%, 4 (36.5%) >=50%. 9 (75%) patients had a TP53 mutation. Two patients had a solitary PIK3CA mutation and were never-smoker female adenocarcinoma patients, one was treated with a PI3Ka-isoform selective inhibitor BYL719 (advanced line), with rapid clinical improvement and partial radiological improvement after 3 months. The only factor showing a statistically significant difference between groups A and B was tumour histology (more adenocarcinoma patients in group B, 83% vs. 17%, P<0.0001). Group A patients had a shorter median overall survival compared with group C (9 months vs. 20 months, P=0.39).
Conclusions
Most patients with PIK3CA mutations without other established driver mutations did not show classical driver mutation characteristics. However, two patients with solitary mutations had these characteristics. One of these two patients responded clinically and partially radiologically to targeted therapy, raising the possibility for PIK3CA mutations being a driver mutation in such cases.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Sheba Medical Center, Hadassah Medical Center.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.