Abstract The impact of KRAS mutation subtypes on treatment response to first‐line immunochemotherapy in advanced lung adenocarcinoma (LUAD) remains uncertain. This study evaluated treatment efficacy across KRAS subtypes and examined the role of programmed death‐ligand 1 (PD‐L1) expression and co‐mutations. We retrospectively analyzed 335 patients with advanced KRAS‐mutant LUAD treated with first‐line immunochemotherapy between 2018 and 2022 at two centers. Patients were categorized into G12A ( n = 36), G12C ( n = 116), G12D ( n = 62), G12V ( n = 56), and other subtypes ( n = 65). PD‐L1 tumor proportion score (TPS) was stratified as <1%, 1–49%, or ≥50%. Endpoints included progression‐free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Median PFS in the overall cohort was 8.6 months, with an ORR of 34.0% and a DCR of 87.8%. Median PFS did not differ significantly among KRAS subtypes ( p = .617), nor within PD‐L1 TPS groups: <1% ( p = .740), 1–49% ( p = .652), and ≥50% ( p = .481). In the major subtypes (G12A, G12C, G12D, and G12V), PD‐L1 expression showed no significant association with PFS. STK11 co‐mutations were enriched in G12C, G12V, and other subtypes ( p = .004) and correlated with shorter PFS ( p = .006). In conclusion, first‐line immunochemotherapy yields comparable efficacy across KRAS subtypes, independent of PD‐L1 expression. Within the major subgroups (G12A, G12C, G12D, and G12V), PD‐L1 levels were not predictive of PFS. STK11 co‐mutations were enriched in G12C, G12V, and other subtypes and were associated with shorter PFS.
Jin et al. (Tue,) studied this question.