Escudier Bernard, Molinie Vincent, Bracarda Sergio, Maroto Pablo, Szczylik Cezary, Nathan Paul, Negrier Sylvie, Weiss Claudia, Porta Camillo, Grünwald Viktor, Albiges Laurence
Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif, France.
Laboratoire d'Anatomie et Cytologie Pathologiques, CHU La Meynard, BP 632, 97261, Fort-de-France, Cedex, France.
Eur J Cancer. 2016 Dec;69:226-235. doi: 10.1016/j.ejca.2016.08.004. Epub 2016 Sep 24.
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).
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.
Analysis sets included safety (N = 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%).
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.
乳头状组织学类型占肾细胞癌（RCC）的10% - 15%，该亚型患者的治疗选择有限。RAPTOR（欧洲晚期乳头状肿瘤项目中的RAD001；ClinicalTrials.gov，NCT00688753）研究评估了一线依维莫司用于乳头状转移性肾细胞癌（mRCC）患者的疗效。
这项2期试验纳入了先前未接受过治疗的1型或2型乳头状mRCC患者。通过中心审查确认乳头状组织学类型，且对每位患者均进行了审查。患者每日口服依维莫司10 mg，直至疾病进展或出现不可接受的毒性反应。主要终点是符合方案（PP）人群中前44例患者6个月时的无进展生存率（PFS）。次要终点包括PFS、肿瘤反应、总生存期（OS）和安全性。
分析集包括安全性人群（N = 92；100%）、意向性治疗（ITT）人群（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）。78%的患者确认了乳头状组织学类型（1型，32%；2型，64%；信息缺失，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%的患者病情稳定，中位OS为21.4个月（95% CI 15.4 - 28.4）。在1型或2型组织学类型的患者中，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 - 不可估计）和24.2个月（95% CI 15.8 - 32.8）。常见的≥2级不良事件为乏力（13%）、贫血（7%）和疲劳（5%）。
这项针对乳头状mRCC的大型前瞻性研究结果表明，依维莫司为该患者群体带来了一定的临床益处，并凸显了对这种罕见肿瘤进行中心病理审查的必要性。
