Avelumab combination improves long-term efficacy in advanced kidney cancer compared with sunitinib

根据发表的3期JAVELINRenal Results from the 101 trial (NCT02684006) showed that avelumab (Bavencio) combined with axitinib (Inlyta) did not significantly improve overall survival (OS) compared with sunitinib (Sunitinib) in patients with advanced renal cell carcinoma (RCC), but the combination treatment also had benefits in other long-term efficacy areas.

The median follow-up times of the avelumab combination group and sunitinib group were 73.7 months and 73.6 months respectively. The median OS of the overall population was 44.8 months respectively ( 95%CI，39.7-51.1）和38.9个月（95%CI，31.4-45.2）（HR，0.88；95%CI，0.749-1.039；P=0.0669）。 In patients with PD-L1-positive disease, the median OS were 43.2 months (95% CI, 36.5-51.7) and 36.2 months, 95% CI, 29.8-44.2 (HR, 0.86; 95% CI, 0.701-1.057; P=0.0755).

Data showed that compared with sunitinib, avelumab/axitinib significantly prolonged progression-free survival (PFS) in the overall population (HR, 0.66; 95% CI, 0.566-0.769) and PD-L1-positive population (HR: 0.57; 95% CI: 0.469-0.697). Additionally, the confirmed objective response rate (ORR) was 59.7% (95% CI, 55.0%-64.3%) in the entire population and 32.0% (95% CI: 27.7%-36.5%) in the PD-L1-positive population (odds ratio [OR], 3.226; 95% CI=2.406-4.279 ; P<.0001), in the PD-L1-positive population, the rate was 64.8% (95%CI-58.8%-70.5%), while the rate was 31.4% (95%CI/26.1%-37.1%) (OR, 4.197; 95%CI-2.863-6.021; P<-0001).

最终OS分析倾向于阿维鲁单抗[加]阿替尼与舒尼替尼，但差异并未达到预先指定的显著性界限。阿维鲁单抗（加）阿替尼显著改善了每位研究者的PFS和ORR评估，与之前的分析一致。总之，JAVELINRenal 101试验的最终分析结果显示了长期疗效益处、可控的安全性和稳定的治疗质量。 [晚期]肾细胞癌患者的一线阿维鲁单抗[加]阿昔替尼生活。

在开放标签的国际3期JAVELINRenal In the 101 trial, 886 patients were randomly assigned to receive avelumab 10 mg/kg intravenously every 2 weeks plus axitinib 5 mg orally twice daily (n=442) or sunitinib 50 mg orally once daily (t=444).该试验的主要终点是根据盲法独立中央审查（BICR）的PFS和PD-L1阳性疾病患者的OS。次要终点包括总体人群的PFS和OS、ORR、反应持续时间（DOR）、安全性和患者报告的结局（PRO）。

Patients 18 years and older with histologically or cytologically confirmed advanced or metastatic renal cell carcinoma with clear cellularity and at least 1 measurable lesion according to RECIST v1.1 criteria are eligible to participate in the trial.进入研究的其他要求包括ECOG性能状态为0或1，骨髓、肾和肝功能良好。

In the avelumab/axitinib and sunitinib treatment groups, the median response time in the PD-L1-positive population was 2.7 months (95% CI, 1.1-28.9) and 2.8 months (95% CI, 1.2-37.5), respectively, and the overall population median response time was 2.8 months. Additionally, the median DOR per arm was 19.3 months (95% CI, 15.1-22.3) in the PD-L1-positive group compared with 9.7 months (95% CI, 7.0-16.6) in the PD-L1-negative group, and 19.4 months (95% CI, 16.4-22.2) compared with 14.5 months (95% CI, 8.7-16.6) in the overall population.

More than90% of patients in each treatment group completed the EuroQol 5 Dimensions 5 Levels and Functional Assessment of Cancer Therapy Renal Cancer Symposium Index - a 19-item version of the instrument for most periods in the study.与这些项目相关的评分在治疗期间通常是稳定的，研究人员观察到两组之间没有显著差异。

Avelumab/96.8% and 96.8% in the axitinib and sunitinib groups, respectively, experienced any treatment-related adverse effect (TRAE), and 66.8% and 61.5% of patients, respectively, reported grade 3 or higher events. Six patients in the avelumab/axitinib group died of unknown causes (n=4), sudden death (n=1), and myocarditis (n=1; one patient in the sunitinib group died due to disease progression. 50.7% of patients receiving avelumab Immune-related toxicities were reported in anti-axitinib-treated patients, with 14.7% experiencing grade 3 or higher. In addition, 15.4% of patients in this group required high-dose corticosteroids.

Reference materials:https://www.cancernetwork.com/view/avelumab-combo-improves-long-term-efficacy-vs-sunitinib-in-advanced-rcc