Open-label phase 2 trial of first-line everolimus monotherapy in patients with papillary metastatic renal cell carcinoma: RAPTOR final analysis
Open-label phase 2 trial of first-line everolimus monotherapy in patients with papillary metastatic renal cell carcinoma: RAPTOR final analysis
复制标题
DOI：
10.1016/j.ejca.2016.08.004
复制
发表时间：
2016-12-01
影响因子：
8.4
通讯作者：
Albiges, Laurence
中科院分区：
文献类型：
--
作者：
Escudier, Bernard;Molinie, Vincent;Albiges, Laurence
背景：乳头状组织学占肾细胞癌（RCC）的10-15%，这种亚型患者的治疗选择有限。RAPTOR（RAD 001 in Advanced Papillary Tumor Program in Europe; ClinicalTrials.gov，NCT 00688753）研究评估了一线依维莫司在乳头状转移性RCC（mRCC）患者中的应用。中心审查确认了乳头状组织学，并对每例患者进行了检查。患者口服依维莫司10 mg，每日一次，直至疾病进展或出现不可接受的毒性。主要终点是符合方案（PP）人群中前44例患者的6个月无进展生存（PFS）率。次要终点包括PFS、肿瘤反应、总生存期（OS）和safety.Findings：分析集包括安全性（NZ 92; 100%）、意向治疗（ITT）（n=88）和PP人群（n = 46）。在安全性人群中，大多数患者为男性（78%），平均年龄为60岁（范围23-84岁）。在78%的患者中证实了乳头状组织学（1型，32%; 2型，64%;缺失信息，4%）。6个月时的PFS率为34%（80%置信区间[CI] 25-45）。在ITT人群中，中位PFS为4.1个月（95% CI 3.6-5.5），65%的患者达到疾病稳定，中位OS为21.4个月（95% CI 15.4-28.4）。在1型或2型组织学患者中，中位PFS分别为7. 9个月（95% CI 2. 1 - 11. 0）和5. 1个月（95% CI 3. 3 - 5. 5），中位OS分别为28. 0个月（95% CI 7. 6-无法估计）和24. 2个月（95% CI 15. 8 - 32. 8）。常见的> 2级不良事件是虚弱（13%）、贫血（7%）和疲劳（5%）。解释：在乳头状mRCC中的这一大型前瞻性研究的结果表明，依维莫司为这一患者群体提供了一些临床益处，并强调了对这种罕见肿瘤进行中心病理学审查的必要性。(C)2016爱思唯尔有限公司版权所有
Background: Papillary histology accounts for 10-15% of renal cell carcinoma (RCC), and treatment options for patients with this subtype are limited. The RAPTOR (RAD001 in Advanced Papillary Tumor Program in Europe; ClinicalTrials.gov, NCT00688753) study evaluated first-line everolimus in patients with papillary metastatic RCC (mRCC).Methods: This phase 2 trial enrolled previously untreated patients with type 1 or type 2 papillary mRCC. Papillary histology was confirmed by central review and was performed for every patient. Patients received oral everolimus 10 mg once daily until disease progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS) rate at 6 months among the first 44 patients of the per protocol (PP) population. Secondary end-points included PFS, tumour response, overall survival (OS), and safety.Findings: Analysis sets included safety (NZ 92; 100%), intent-to-treat (ITT) (n=88), and PP populations (n = 46). In the safety population, most patients were men (78%) and the mean age was 60 years (range 23-84). Papillary histology was confirmed in 78% of patients (type 1, 32%; type 2, 64%; missing information, 4%). PFS rate at 6 months was 34% (80% confidence interval [CI] 25-45). In the ITT population, median PFS was 4.1 months (95% CI 3.6-5.5), 65% of patients achieved stable disease, and median OS was 21.4 months (95% CI 15.4-28.4). Among patients with type 1 or type 2 histology, median PFS was 7.9 months (95% CI 2.1 -11.0) and 5.1 months (95% CI 3.3-5.5), respectively, and median OS was 28.0 months (95% CI 7.6-not estimable) and 24.2 months (95% CI 15.8-32.8), respectively. Common grade > 2 adverse events were asthenia (13%), anaemia (7%), and fatigue (5%).Interpretation: Results of this large prospective study in papillary mRCC demonstrated that everolimus provides some clinical benefit to this patient population and highlight the need for central pathological review of this rare tumour. (C) 2016 Elsevier Ltd. All rights reserved.