Everolimus Plus Octreotide Long‐Acting Repeatable in Patients With Colorectal Neuroendocrine Tumors: A Subgroup Analysis of the Phase III RADIANT‐2 Study. (21st December 2012)

• Record Type: Journal Article
• Authors: Castellano, Daniel; Bajetta, Emilio; Panneerselvam, Ashok; Saletan, Stephen; Kocha, Walter; O'Dorisio, Thomas; Anthony, Lowell B.; Hobday, Timothy
• Is Part Of: Oncologist. Volume 18:Number 1(2013)
• Page Start: 46
• Page End: 53
• Publication Date: 2012-12-21
• Subjects: Colorectal cancer -- Everolimus -- Neuroendocrine tumors -- Octreotide -- LAR; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2012-0263
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract : Introduction: The incidence of colorectal neuroendocrine tumors (NETs) is increasing, and patients with this disease have particularly poor prognoses. Treatment options are limited, and survival times have not improved in the past decade. Methods: A post hoc analysis of the efficacy and tolerability of everolimus plus octreotide long‐acting repeatable (LAR) was conducted in patients with colorectal NETs enrolled in the phase III RAD001 in Advanced Neuroendocrine Tumors, Second Trial (RADIANT‐2) study. The primary endpoint (progression‐free survival [PFS]), secondary endpoints (including objective response rate), and safety were assessed. Results: Patients with colorectal NETs receiving everolimus plus octreotide LAR had a significantly longer median PFS (29.9 months; n = 19) than did those receiving placebo plus octreotide LAR (6.6 months; n = 20). Everolimus plus octreotide LAR treatment also significantly reduced the risk for disease progression (hazard ratio: 0.34; 95% confidence interval: 0.13–0.89; p = .011). Although no objective responses were observed, tumor shrinkage was more frequently noted in the everolimus plus octreotide LAR arm than in the placebo plus octreotide LAR arm (67% vs. 37%, respectively). The combination of everolimus plus octreotide LAR was generally well tolerated by patients with colorectal NETs; rash and stomatitis were the most commonly reported adverse events. Conclusions: Everolimus plus octreotide LAR treatment had significant benefits and improved outcomes for patients with advanced colorectal NETs compared with placebo plus octreotide LAR treatment. Results of this exploratory analysis are consistent with those reported from the RADIANT‐2 primary analysis. These findings support additional investigations of everolimus plus octreotide LAR in patients with colorectal NETs. Abstract : A post hoc analysis of the efficacy and tolerability of everolimus plus octreotide long‐acting repeatable (LAR) was conducted in patients with colorectal neuroendrocrine tumors (NETs) enrolled in the phase III RADIANT‐2 study. Significant benefits and improved outcomes were demonstrated for patients with advanced colorectal NETs who were treated with everolimus plus octreotide LAR. Abstract : 摘要 引言 . 结直肠神经内分泌肿瘤（NET）发病率不断增加，患者预后特别差。该病治疗方法局限，近十年来，其生存时间未见延长。 方法 . 在III期RAD001晚期神经内分泌肿瘤第二次试验（RADIANT‐2）入组的结直肠NET患者中，开展一项 post hoc 分析，评估依维莫司联合长效缓释（LAR）奥曲肽的有效性及耐受性。评估主要终点[无进展生存（PFS）]、次要终点（包括客观缓解率）和安全性。 结果 . 接受依维莫司联合奥曲肽LAR的结直肠NET患者，中位PFS（29.9个月， n =19）显著长于安慰剂联合奥曲肽LAR组（6.6个月， n =20）。依维莫司联合奥曲肽LAR同时显著降低了疾病进展的风险（风险比：0.34；95%可信区间：0.13∼0.89； P =0.011）。虽然未见客观缓解，但依维莫司联合奥曲肽LAR组的肿瘤退缩多于安慰剂联合奥曲肽LAR组（分别为67% vs. 37%）。此外，依维莫司联合奥曲肽LAR耐受性良好；皮疹和口腔炎是最常见的不良事件。 结论 . 与安慰剂联合奥曲肽LAR组相比，晚期结直肠NET患者接受依维莫司联合奥曲肽LAR后获益显著且转归改善。本项探索性分析结果与RADIANT‐2总体分析结果相一致。这些结果支持在结直肠NET患者中进一步开展依维莫司联合奥曲肽LAR的研究。