Race-associated clinicogenomic predictors in non-small cell lung cancer treated with immune checkpoint inhibitors.

Abstract

8557 Background: PD-L1 low and STK11 mutation associate with immune checkpoint inhibitor (ICI) resistance in non-small cell lung cancer (NSCLC), but appear differentially expressed among racial ethnic groups. This has not been validated in large, diverse studies. Methods: We retrospectively studied NSCLC patients 18 or older, without targetable EGFR or ALK alterations, treated with frontline ICI between January 2014 and February 2020 at MD Anderson Cancer Center and University of Illinois Chicago. We analyzed clinicogenomic and survival characteristics by race/ethnicity. Differences in clinicogenomic predictors were assessed through log-rank and chi-squared comparison of proportions tests. Survival differences were estimated via Kaplan-Meier method. Results: 1694 patients met inclusion criteria, 383 (22.6%) were minorities. Poor performance status (PS 2-3) was most frequent in African American (AA) (32.5%) and Native Alaskan/Hawaiian or American Indian (NAHAI) (27.3%) patients (p=0.005) (Table). Heavy smoking was more frequent in White (50.3%) patients. PD-L1 <1% was most prevalent among Asian (31.3%) and least prevalent among Hispanic/Latino (HL) (15.8%) patients (p=0.001). STK11 mutation rate was most prevalent in AA (14.7%) and least prevalent in HL (6.9%) and Asian (2.5%) patients (p=0.056). Median overall survival (OS) was lower (21.3, 23.5, and 24.3 months) for HL, NAHAI, and AA patients, and higher (25.4 and 30.6 months) for White and Asian patients, respectively (p<0.01). Conclusions: Our dual center study with 22% minority patient representation shows self-reported race can result in biological differences, because of ancestry and/or environmental differences. AA, HL, and NAHAI patients had lower rates of heavy smoking and different clinicogenomic patterns than White patients. AA tended towards higher prevalence of STK11 mutation—while not statistically significant, it was overall not highly represented in the sample. In line with these poor prognostic factors, AA had statistically significant lower median overall survival (OS) than their White and Asian counterparts. Asians had the lowest rates of heavy smoking and STK11 mutation, highest rates of PD-L1<1%, and highest median OS. HL had the lowest OS, with low prevalence of PD-L1<1% and STK11 mutation – future studies should evaluate other clinicogenomic factors to determine potential culprits. White Black or African American (AA) Hispanic or Latino (HL) Asian Native Alaskan/Hawaiian or American Indian (NAHAI) p-value Total cohort n=1694, No. (%) 1311 (77.4) 191 (11.3) 101 (6.1) 80 (4.7) 11 (0.5) ECOG PS 2-3 at ICI start 267 (20.4) 62 (32.5) 23 (22.8) 20 (25.0) 3 (27.3) 0.005 20+ Pack Years Smoking 659 (50.3) 77 (40.3) 26 (25.7) 19 (23.8) 5 (45.5) 4.9 ×10 -9 PD-L1 <1% 317 (24.2) 47 (24.6) 16 (15.8) 25 (31.3) 1 (9.1) 0.001 STK11 mut 129 (9.8) 22 (14.7) 7 (6.9) 2 (2.5) 1 (9.1) 0.056 Median OS (mo) 25.4 24.3 21.3 30.6 23.5 < 0.01