Equalizing prognostic disparities in KRAS-mutated stage III NSCLC patients: addition of durvalumab to combined chemoradiotherapy improves survival.

Stage III non-small cell lung cancer (NSCLC) is a heterogeneous group and identification of subgroups with differential treatment responses is crucial. Addition of durvalumab to concurrent chemoradiotherapy (cCRT) has previously been shown to improve survival outcomes. Meanwhile, subgroups harboring KRAS mutations have been shown to have worse prognosis. We investigated whether KRAS mutational status may affect survival outcomes after adjuvant durvalumab following cCRT in stage III NSCLC. In this multi-center retrospective study, we present a real-world dataset of all stage III NSCLC patients treated with curative-intent cCRT with molecular assessment, between 2016 and 2021 in the Västra Götaland Region of western Sweden. The study period includes the standard practice prior to the introduction of durvalumab, enabling evaluation of the potential impact of immune checkpoint blockade (ICB). Primary study outcomes were overall survival (OS) and progression free survival (PFS). We identified 145 patients who received cCRT with curative intent, and 32 % harbored an activating mutation in the KRAS gene (KRAS; n = 46). Compared to patients with wild-type KRAS (KRAS; n = 99), KRAS had worse OS (p = 0.047) and PFS (p = 0.038). This finding persisted on multivariate analysis with OS (HR 1.703, 95 % CI 1.074-2.702, p = 0.024) and PFS (HR 1.628, 95 % CI 1.081-2.453, p = 0.020). Within the subgroup that received cCRT alone, KRAS patients (n = 35) exhibited worse OS (p = 0.036) and PFS (p = 0.037) compared with KRAS (n = 35). However, among those who received additional durvalumab after cCRT (KRAS; n = 99. KRAS; n = 11) there were no significant differences in OS (0.788) or PFS (0.855) between the groups. KRAS mutations are a negative prognostic factor after cCRT in stage III NSCLC, and the addition of durvalumab ameliorates the negative impact of harboring this mutation.