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

Abstract Introduction Stage III non-small cell lung cancer (NSCLC) is heterogeneous and identification of subgroups with differential responses is crucial to optimize treatment. 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. Methods In this retrospective study, we present a real-world dataset of all stage III NSCLC patients treated with cCRT with a curative intent and molecularly assessed between 2016-2021 in West Sweden. Primary study outcomes were overall survival (OS) and progression free survival (PFS). Results We identified 145 patients receiving cCRT with a curative intent, 32% harbored an activating mutation in the KRAS gene (KRAS MUT ). Compared to KRAS wild-type (KRAS WT ), KRAS MUT had a worse OS ( p =0.047) and PFS ( p =0.038). The 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). After the addition of durvalumab to cCRT, there were no longer any significant differences between KRAS WT and KRAS MUT in OS or PFS. Conclusions KRAS mutations are a negative prognostic factor after cCRT in stage III NSCLC, and the addition of durvalumab equalizes the negative impact of harboring this mutation.