PIK3CA (phosphatidylinositol-3 kinase) mutations have been found in multiple tumor sites including NSCLC among others, in the latter the frequency range between 2-7%. It has been related to cell growth, metabolism and survival as part of the PI3K-AKT-mTOR pathway. As part of this pathway, it may be amenable to targeted therapies which target mTOR. We conducted a retrospective study using the institutional Glans Look Lung Cancer Research (GLR) database, which contains demographics, treatment and outcome data. A cohort was extracted from the GLR comprised of patients diagnosed with a non-small cell cancer, between 2011 and 2020, with a PIK3CA mutation, complete pathology and molecular analysis. They were stratified by demographics (sex, age, ECOG, etc.), tumor characteristics (PIK3CA mutation type, associated co-mutations, PD-L1 status) and treatment (initial and subsequent treatment, type of therapy, etc.). The endpoints were frequency and type PIK3CA mutations, association with co-mutations and impact on treatment efficacy. 25 patients were identified, 56% were female, 70.84 was the median age at diagnosis, 52% were ECOG 1, 48% were Stage IV with 84% being Adenocarcinomas and 52% had confirmed smoking history. By data cut off 36% were still alive.Tabled 1E545KE542KH1047RH1047LPIK3CA (n:25)11 (44%)7 (28%)6 (24%)1 (4%)EGFR (n:9)3 (33.3%)3 (33.3%)3 (33.3%)0Sensitive (Del19, L858R)213Resistance (Exon 20 Insertion)1Intermediate (Exon18/Exon20)11KRAS (n:1)1 (100%)ALK (n:1)1 (100%)ROS-1 (n:1)1 (100%)PD-L1 Expression (n:22)10 (45.4%)6 (27.2%)5 (22.7%)1 (4.5%)High >50% (22.7%)221Low 1-49% (22.7%)311Negative <1% (54.5%)5331 Open table in a new tab 48% of PIK3CA mutations had an associated co-mutation. KRAS and ROS1 were unspecific and not targeted. The median survival on EGFR inhibitors was 24.84m (22.48m including Poziotinib), 27.3m on Alectinib and 10.64m on Immunotherapy. These were affected by comorbidities, performance status and side effects.Tabled 1Stage I (n:2)Stage II (n:2)Stage IIIA (n:3)Stage IIIB (n:5)Stage IIIC (n:1)Stage IVA (n:4)Stage IVB (n:8)Curative Intent1223Surgery/Adjuvant Chemotherapy +/- RT11Radical RT112Concurrent ChemoRT +/- Durvalumab2Recurrence/ProgressionNoYesYesYesTotal (n)113Palliative Setting1122148Declined/No further Tx1121Palliative RT (1st L)1112Chemotherapy (1st L)11Chemo + Pembrolizumab (1st L)1TKI (1st L)11113Gefitinib111Afatinib1111Alectinib1Immunotherapy (1st L)1Nivolumab1PembrolizumabProgression to 1st LNoNoYesYesYesYes2nd Line Tx (n)2112TKI (2nd L)12Immunotherapy (2nd L)11Chemotherapy (2nd L)11Progression to 2nd LYes3rd Line Tx (n)1Alive (n:9 - 36%)1 (50%)2 (100%)2 (66%)01 (100%)03 (37.5%) Open table in a new tab PIK3CA mutations did not follow a specific pattern and, despite being associated with other mutations in almost half the cases, they do not seem to influence treatment response or median survival either with TKI or checkpoint inhibitors. Infrequent mutations need to be further assessed to determine their impact while future research should focus on defining the subgroup where inhibitors of the AKT pathway may prove beneficial.