Race-associated clinicogenomic correlates of outcomes to immune checkpoint inhibitors alone or with chemotherapy in non-small cell lung cancer (NSCLC).

Abstract

8567 Background: PD-L1 low and STK11 mutations are associated with immune checkpoint inhibitor (ICI) resistance in non-small cell lung cancer (NSCLC). It is unclear whether there are differences in clinicogenomic predictors by race and ethnicity. Methods: We retrospectively studied NSCLC patients 18 or older, without targetable EGFR or ALK alterations, treated with frontline combination chemotherapy with ICI (ICI-chemo) or ICI monotherapy (ICI-mono) between January 2014 and February 2020 at MD Anderson Cancer Center. 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: 1648 patients met inclusion criteria. Poor performance status (PS) frequency was statistically significantly different among groups, highest in African American (AA) (30.7%) and Native Alaskan/Hawaiian or American Indian (NAHAI) (30%) patients (Table). Steroid prescription within one month of ICI start was also more frequent in AA (46.4%) and NAHAI (40%) patients. However, heavy smoking was more frequent in White (62%) patients. Mutation rates were statistically significantly different for KRAS and STK11 but not TP53 (Table). KRAS mutations were most frequent in White (24.7%) and AA patients (24.2%). STK11 mutations were most frequent in AA (14.4%) patients. TP53 mutations were most frequent in HL and Black (43.6%, 41.8%) patients. Median overall survival (OS) was lower (21.3 and 24.5 months) for HL and NAHAI patients and higher (25.4, 26.4, and 30.7 months) for White, Black, and Asian patients, though not statistically significantly different (Table). Conclusions: AA and HL patients had lower rates of heavy smoking but higher rates of poor genomic prognostic factors. Asian patients had the lowest rates of heavy smoking, KRAS, TP53, and STK11 mutations, but the highest rates of PD-L1 <1%. Despite several traditional clinicogenomic prognostic factors being poor for minority racial/ethnic groups, OS difference was not statistically significant. White Black or African American (AA) Hispanic or Latino (HL) Asian Native Alaskan/Hawaiian or American Indian (NAHAI) p-value Total cohort n=1648, No. (%) 1305 (79.2) 153 (9.3) 101 (6.1) 79 (4.8) 10 (0.6) ECOG PS 2-3 at ICI start 265 (20.3) 47 (30.7) 23 (22.8) 20 (25.3) 3 (30) 0.003 Steroids within 1 mo of ICI start 480 (36.8) 71 (46.4) 39 (38.6) 29 (36.7) 4 (40) 0.02 20+ Pack Years Smoking 652 (62) 63 (50) 26 (46.4) 18 (43.9) 5 (55.6) 0.001 PD-L1 <1% 313 (24) 31 (20.3) 16 (15.8) 25 (31.6) 1 (10) 0.01 KRAS mut 322 (24.7) 37 (24.2) 23 (22.8) 6 (7.6) 4 (40) 0.001 TP53 mut 486 (37.2) 64 (41.8) 44 (43.6) 25 (31.6) 4 (40) 0.1 STK11 mut 129 (9.9) 22 (14.4) 7 (6.9) 2 (2.5) 1 (10) 0.005 Median OS (mo) 25.4 26.4 21.3 30.7 24.5 0.2