度伐利尤单抗对放化疗治疗的 III 期 NSCLC 患者的局部区域控制的影响及对 KEAP1-NFE2L2 突变型肿瘤的影响。
The Impact of Durvalumab on Local-Regional Control in Stage III NSCLCs Treated With Chemoradiation and on KEAP1-NFE2L2-Mutant Tumors.
机构信息
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
出版信息
J Thorac Oncol. 2021 Aug;16(8):1392-1402. doi: 10.1016/j.jtho.2021.04.019. Epub 2021 May 13.
INTRODUCTION
KEAP1-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.
METHODS
Patients 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.
RESULTS
We 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).
CONCLUSIONS
Durvalumab after cCRT significantly improves local-regional control and reduces LRF in chemoradiation-resistant KEAP1-NFE2L2-mutant NSCLC tumors.
简介
KEAP1-NFE2L2 突变的 NSCLC 对放化疗具有耐药性，并且在接受同期放化疗（cCRT）后局部区域复发（LRF）的风险较高。为了阐明度伐利尤单抗对局部区域控制的影响，我们评估了接受 cCRT 联合或不联合度伐利尤单抗治疗的 NSCLC 患者的 LRF 情况。
方法
评估了接受 cCRT 或 cCRT 联合度伐利尤单抗治疗且进行肿瘤基因组分析的 III 期 NSCLC 患者。评估了有和无 KEAP1-NFE2L2 突变肿瘤患者的 LRF 发生率和结局。
结果
我们分析了 120 例连续患者（cCRT 单药治疗，n=54；cCRT 联合度伐利尤单抗治疗，n=66）。cCRT 单药治疗组的 LRF 事件明显多于 cCRT 联合度伐利尤单抗治疗组，12 个月 LRF 发生率分别为 39%（95%CI：24%-54%）和 18%（95%CI：8%-28%）（p=0.002）。在 cCRT 单药治疗组和 cCRT 联合度伐利尤单抗治疗组中，分别有 20 例（37%）和 18 例（27%）患者存在 KEAP1-NFE2L2 突变肿瘤。在 cCRT 单药治疗组中，KEAP1-NFE2L2 突变肿瘤患者的局部区域控制更差（p=0.015），并且多变量分析显示 KEAP1-NFE2L2 突变与 LRF 相关（风险比=3.9，95%CI：1.6-9.8，p=0.003）。然而，当接受 cCRT 联合度伐利尤单抗治疗时，KEAP1-NFE2L2 突变肿瘤患者的 LRF 结局相似（p=0.541），突变状态与 LRF 无关（p=0.545）。在存在 KEAP1-NFE2L2 突变肿瘤的患者中，与 cCRT 单药治疗相比，cCRT 联合度伐利尤单抗显著降低了 LRF 的发生率：12 个月 LRF 发生率分别为 62%（95%CI：40%-84%）和 25%（95%CI：4%-46%）（p=0.021）。
结论
cCRT 后接受度伐利尤单抗治疗可显著改善放化疗耐药的 KEAP1-NFE2L2 突变 NSCLC 肿瘤的局部区域控制，并降低 LRF 发生率。
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