Impact of high-risk genomic alterations on survival outcomes in patients with stage III non–small cell lung cancer treated with chemoradiation and consolidation durvalumab.

e20042 Background: Concurrent chemoradiation (CCRT) followed by programmed death ligand-1 (PD-L1) checkpoint inhibition with durvalumab (D) is standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). A subset of patients with resectable stage III disease also receive this regimen when surgery is not pursued. Several genomic alterations have been associated with worse outcomes in NSCLC patients treated with PD-L1 pathway inhibitors. We sought to determine whether certain high risk genomic alterations impact overall survival (OS) and progression-free survival (PFS) in these patients. Methods: We retrospectively reviewed the outcomes of patients receiving care at the University of Minnesota with stage IIIA-C NSLC who were treated with CCRT+D between 2017 and 2023. A subset of these patients had next generation sequencing (NGS) of their tumors prior to initiation of chemotherapy. PFS and OS were calculated for patients from the time of chemotherapy initiation. High risk genomic alterations (HRGA) were defined as pathogenic variants of KRAS , TP53 , KEAP1 , STK11 , ALK , EGFR , or ROS1 . Kaplan-Meier analysis was used to calculate PFS and OS for patients with a HRGA compared to patients without these mutations. Results: Among 115 patients in the cohort, 79 had NGS data available from biopsy samples or ctDNA samples obtained prior to starting chemotherapy and were considered in this analysis. 30 patients had at least one HRGA (16 KRAS , 6 TP53 , 1 KEAP1 , 1 STK11 , 1 KEAP1 + STK11 , 1 KRAS + TP53 , 1 KRAS + KEAP1 , 1 EGFR , 1 EGFR + TP53 , 1 ALK ). PFS was 887 days in the HRGA group and 587 days in the non-HRGA group (p-value=0.4). OS was 1,110 days in the HRGA group and 938 days in the non-HRGA group (p-value=0.3). Conclusions: In our cohort of stage III NSCLC patients treated with CCRT+D, we did not observe a statistical difference in OS or PFS among patients with a HRGA compared to those without. While our relatively small sample size limits the ability to draw firm conclusions, these data suggest that presence of these genomic alterations in stage IIIA-C NSLC patients should not preclude treatment with CCRT+D. Baseline characteristics and survival outcomes of patients in our cohort. Characteristic Overall (N = 79) 1 No mutations (N = 49) 1 Any mutations (N = 30) 1 p-value 2 PFS (days) 663 (787) 587 (690) 887 (994) 0.4 OS (days) 1,025 (900) 938 (879) 1,110 (855) 0.3 Age (years) 69 (14)Unknown = 2 70 (12)Unknown = 0 68 (12)Unknown = 2 0.4 PD-L1 status 0.13 PD-L1 &lt;1 PD-L1 &gt;= 1 PD-L1 unknown 24 (34%)46 (66%)9 17 (41%)24 (59%)8 7 (24%)22 (76%)1 Histology &lt;0.001 Squamous cell carcinoma 33 (42%) 28 (57%) 5 (17%) Adenocarcinoma 41 (52%) 18 (37%) 23 (77%) Other NSCLC subtype <jats:td