The Impact of Durvalumab on Local-Regional Control in Stage III NSCLCs Treated With Chemoradiation and on KEAP1-NFE2L2-Mutant Tumors

Abstract

IntroductionKEAP1-NFE2L2-mutant NSCLCs are chemoradiation resistant and at high risk for local-regional failure (LRF) after concurrent chemoradiation (cCRT). To elucidate the impact of durvalumab on local-regional control, we evaluated LRF in patients with NSCLC treated with cCRT with and without durvalumab. MethodsPatients with stage III NSCLC treated with cCRT or cCRT and durvalumab who underwent tumor genomic profiling were evaluated. The incidence of LRF and outcomes of patients with and without KEAP1-NFE2L2-mutant tumors were evaluated. ResultsWe analyzed 120 consecutive patients (cCRT alone, n = 54; cCRT and durvalumab, n = 66). Patients treated with cCRT alone had significantly more LRF events compared with those treated with cCRT and durvalumab, with 12-month LRF incidence of 39% (95% confidence interval [CI]: 24%–54%) and 18% (95% CI: 8%–28%), respectively (p = 0.002). Among patients treated with cCRT alone and cCRT and durvalumab, 20 patients (37%) and 18 patients (27%), respectively, had KEAP1-NFE2L2-mutant tumors. In patients treated with cCRT alone, those with KEAP1-NFE2L2-mutant tumors had worse local-regional control (p = 0.015), and on multivariate analysis, KEAP1-NFE2L2 mutation predicted for LRF (hazard ratio = 3.9, 95% CI: 1.6–9.8, p = 0.003). Nevertheless, patients with and without KEAP1-NFE2L2-mutant tumors had similar LRF outcomes (p = 0.541) when treated with cCRT and durvalumab, and mutational status did not predict for LRF (p = 0.545). Among those with KEAP1-NFE2L2-mutant tumors, cCRT and durvalumab significantly reduced the incidence of LRF compared with cCRT alone: 12-month LRF incidence of 62% (95% CI: 40%–84%) versus 25% (95% CI: 4%–46%), respectively (p = 0.021). ConclusionsDurvalumab after cCRT significantly improves local-regional control and reduces LRF in chemoradiation-resistant KEAP1-NFE2L2-mutant NSCLC tumors.