C 反应蛋白与avelumab 联合 axitinib 治疗晚期肾细胞癌疗效的相关性：JAVELIN Renal 101 的长期随访结果。
Association of C-reactive protein with efficacy of avelumab plus axitinib in advanced renal cell carcinoma: long-term follow-up results from JAVELIN Renal 101.
机构信息
Department of Urology, Department of Molecular Oncology, Niigata University Graduate School of Medicine, Niigata, Japan.
Department of Medical Oncology, Royal Marsden NHS Foundation Trust, London, UK.
出版信息
ESMO Open. 2022 Oct;7(5):100564. doi: 10.1016/j.esmoop.2022.100564. Epub 2022 Aug 28.
BACKGROUND
C-reactive protein (CRP) is an important prognostic and predictive factor in advanced renal cell carcinoma (aRCC). We report the association of CRP levels at baseline and early after treatment with efficacy of avelumab plus axitinib or sunitinib from the phase III JAVELIN Renal 101 trial.
PATIENTS AND METHODS
Patients were categorized into normal (baseline CRP <10 mg/l), normalized (baseline CRP ≥10 mg/l and ≥1 CRP value decreased to <10 mg/l during 6-week treatment), and non-normalized (CRP ≥10 mg/l at baseline and during 6-week treatment) CRP groups. Progression-free survival and best overall response from the second interim analysis and overall survival (OS) from the third interim analysis were assessed.
RESULTS
In the avelumab plus axitinib and sunitinib arms, respectively, 234, 51, and 108 patients and 232, 36, and 128 patients were categorized into normal, normalized, and non-normalized CRP groups. In respective CRP groups, objective response rates [95% confidence interval (CI)] were 56.0% (49.4% to 62.4%), 66.7% (52.1% to 79.2%), and 45.4% (35.8% to 55.2%) with avelumab plus axitinib and 30.6% (24.7% to 37.0%), 41.7% (25.5% to 59.2%), and 19.5% (13.1% to 27.5%) with sunitinib; complete response rates were 3.8%, 11.8%, and 0.9% and 3.0%, 0%, and 1.6%, respectively. Median progression-free survival (95% CI) was 15.2 months (12.5-21.0 months), not reached (NR) [11.1 months-not estimable (NE)], and 7.0 months (5.6-9.9 months) with avelumab plus axitinib and 11.2 months (8.4-13.9 months), 11.2 months (6.7-13.8 months), and 4.2 months (2.8-5.6 months) with sunitinib; median OS (95% CI) was NR (42.2 months-NE), NR (30.4 months-NE), and 23.0 months (18.4-33.1 months) and NR (39.0 months-NE), 39.8 months (21.7-NE), and 19.1 months (16.3-25.3 months), respectively. Multivariate analyses demonstrated that normalized or non-normalized CRP levels were independent factors for the prediction of objective response rate or OS, respectively, with avelumab plus axitinib.
CONCLUSIONS
In patients with aRCC, CRP levels at baseline and early after treatment may predict efficacy with avelumab plus axitinib.
背景
C 反应蛋白（CRP）是晚期肾细胞癌（aRCC）的重要预后和预测因素。我们报告了来自 III 期 JAVELIN Renal 101 试验的数据，该数据显示在基线和治疗早期 CRP 水平与avelumab 联合阿昔替尼或舒尼替尼的疗效相关。
患者和方法
患者被分为正常（基线 CRP<10mg/l）、正常化（基线 CRP≥10mg/l，且在 6 周治疗期间至少有 1 次 CRP 值下降至<10mg/l）和未正常化（基线和 6 周治疗期间 CRP≥10mg/l）CRP 组。评估第二次中期分析的无进展生存期和最佳总体反应，以及第三次中期分析的总生存期（OS）。
结果
在 avelumab 联合阿昔替尼和舒尼替尼组中，分别有 234、51 和 108 例患者和 232、36 和 128 例患者被分为正常、正常化和未正常化 CRP 组。在各自的 CRP 组中，客观缓解率（95%置信区间（CI））分别为 56.0%（49.4%至 62.4%）、66.7%（52.1%至 79.2%）和 45.4%（35.8%至 55.2%）与 avelumab 联合阿昔替尼，以及 30.6%（24.7%至 37.0%）、41.7%（25.5%至 59.2%）和 19.5%（13.1%至 27.5%）与舒尼替尼；完全缓解率分别为 3.8%、11.8%和 0.9%和 3.0%、0%和 1.6%。中位无进展生存期（95%CI）分别为 15.2 个月（12.5-21.0 个月）、未达到（NR）[11.1 个月-不可估计（NE）]和 7.0 个月（5.6-9.9 个月）与 avelumab 联合阿昔替尼，以及 11.2 个月（8.4-13.9 个月）、11.2 个月（6.7-13.8 个月）和 4.2 个月（2.8-5.6 个月）与舒尼替尼；中位 OS（95%CI）分别为 NR（42.2 个月-NE）、NR（30.4 个月-NE）和 23.0 个月（18.4-33.1 个月）和 NR（39.0 个月-NE）、39.8 个月（21.7-NE）和 19.1 个月（16.3-25.3 个月）。多变量分析表明，正常化或未正常化的 CRP 水平分别是与 avelumab 联合阿昔替尼相关的客观缓解率或 OS 的独立预测因素。
结论
在晚期肾细胞癌患者中，基线和治疗早期的 CRP 水平可能预测 avelumab 联合阿昔替尼的疗效。
Zotero 插件