Outcomes in STK11-, KEAP1-, and KRAS-mutant lung squamous cell carcinoma (LSCC) with use of immune checkpoint inhibitors (ICIs).

Abstract

e20504 Background: Studies have suggested that STK11, KEAP1, and KRAS mutations impact response to ICIs in individuals with lung adenocarcinoma. The effect of these mutations in LSCC is unknown. Methods: We conducted a retrospective analysis from January 1, 2018 through December 31, 2023 evaluating individuals seen in the Indiana University Health System with STK11, KEAP1, or KRAS-mutant advanced LSCC treated with ICI-based therapy. Demographic information and baseline PD-L1 levels were collected. Response to therapy was assessed using standardized real-world criteria. Progression-free survival (PFS) was calculated using the Kaplan-Meier method and compared using a log-rank test. Results: Thirty-one of 316 evaluable patients with LSCC had a mutation in KEAP1, STK11, or KRAS. Twenty-one of those individuals had advanced disease treated with ICIs. Nine of 21 had tumors harboring KEAP1 and/or STK11, 10 had tumors harboring KRAS, and 2 had KRAS + STK11-mutant tumors. The median age was 67 years, 71% (15/21) were male, 86% (18/21) were White, 83% (15/18) had PD-L1 levels ≥1%, and 81% (17/21) were evaluable for response including 11 treated with ICIs + chemotherapy and 6 who received ICIs alone. The overall response rate (ORR) was 65% with 5 individuals having progressive disease (PD), 1 with stable disease (SD), and 11 exhibiting partial response (PR). Those receiving ICIs + chemotherapy had an ORR of 73% (3 PD, 8 PR). The ORR was 50% (2 PD, 1 SD, 3 PR) in the cohort treated with ICIs alone. Among those with KEAP1 and/or STK11 mutations, the ORR was 43% (4 PD, 3 PR). The ORR was 88% for the KRAS-mutant cohort (1 SD, 7 PR) and 50% in the KRAS + STK11 subgroup (1 PD, 1PR). The median PFS was 6.4 months for the entire population, 6.0 months for those treated with ICIs + chemotherapy, and 8.1 months for those receiving ICIs alone. Although the cohort size was limited, individuals with KRAS mutations appeared to have improved PFS compared to those with STK11, KEAP1, or KRAS + STK11 mutations treated with ICI-based therapy (Table 1). Conclusions: STK11, KEAP1, and KRAS mutations impact response to ICIs in individuals with LSCC. There was a trend toward improved ORR and PFS in those with KRAS-mutant LSCC treated with ICI-based therapy compared to those with STK11, KEAP1, or KRAS + STK11-mutations. [Table: see text]