A double-blind placebo-controlled randomized phase II trial assessing the activity and safety of regorafenib in non-adipocytic sarcoma patients previously treated with both chemotherapy and pazopanib

被引：9

作者：

Penel, Nicolas ^{[1
,2
]}

Mir, Olivier ^{[3
]}

Wallet, Jennifer ^{[4
]}

Ray-Coquard, Isabelle ^{[5
]}

Le Cesne, Axel ^{[3
]}

Italiano, Antoine ^{[6
]}

Salas, Sebastien ^{[7
]}

Delcambre, Corinne ^{[8
]}

Bompas, Emmanuelle ^{[9
]}

Bertucci, Francois ^{[10
]}

Saada-Bouzid, Esma ^{[11
]}

Chaigneau, Loic ^{[12
]}

Chevreau, Christine ^{[13
]}

Brodowicz, Thomas ^{[14
]}

Decoupigny, Emilie ^{[4
]}

Vanseymortier, Marie ^{[4
]}

Laroche, Lucie ^{[15
]}

Taieb, Sophie ^{[16
]}

Le Deley, Marie-Cecile ^{[4
,17
]}

Blay, Jean-Yves ^{[5
]}

机构：

[1] Ctr Oscar Lambret, Med Oncol Dept, Lille, France

[2] Lille Univ, Lille Univ Hosp, Lille, France

[3] Gustave Roussy, Med Oncol Dept, Villejuif, France

[4] Ctr Oscar Lambret, Clin Res & Innovat Dept, Lille, France

[5] Ctr Leon Berard, Med Oncol Dept, Lyon, France

[6] Inst Bergonie, Med Oncol Dept, Bordeaux, France

[7] CH La Timone, Med Oncol Dept, Marseille, France

[8] Ctr Francois Baclesse, Med Oncol Dept, Caen, France

[9] Rene Gauducheau, Med Oncol Dept, St Herblain, France

[10] Inst Paoli Calmette, Med Oncol Dept, Marseille, France

[11] Ctr Antoine Lacassagne, Med Oncol Dept, Nice, France

[12] Hop St Jacques, Med Oncol Dept, Besancon, France

[13] Inst Univ Cancerol Toulouse, Med Oncol Dept, Toulouse, France

[14] Med Univ Vienna, Gen Hosp, Vienna, Austria

[15] Labeled Datactr, Caen, France

[16] Ctr Oscar Lambret, Radiol Dept, Lille, France

[17] Univ Paris Saclay, Univ Paris Sud, INSERM, CESP,UVSQ, Villejuif, France

来源：

EUROPEAN JOURNAL OF CANCER | 2020年 / 126卷

关键词：

Angiogenesis; Pazopanib; Soft tissue sarcoma; Randomized phase II trial; Regorafenib; SOFT-TISSUE SARCOMA; EFFICACY; FAILURE; PALETTE;

D O I：

10.1016/j.ejca.2019.12.001

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Metastatic soft tissue sarcomas (STSs) management remains an unmet medical need. We assessed the activity and safety of regorafenib in patients with metastatic non-adipocytic STS who were previously treated with both chemotherapy and pazopanib. Patients and methods: This double-blind, placebo-controlled, multicenter comparative randomized phase II trial included patients with histologically proven advanced and inoperable STS. Patients receiving placebo were offered optional cross-over for centrally confirmed disease progression. Primary end-point was centrally reviewed Response Evaluation Criteria in Solid Tumours-based progression-free survival (PFS), analysed on the intent-to-treat data set. In total, 24 events were required for 90% power, hazard ratio (HR) = 0.33 (median PFS, 3.6 versus 1.2 months), and 1-sided alpha = 0.1 (ClinicalTrials.gov, NCT01900743). Results: From December 2015 to October 2017, 37 patients were randomized; 18 to regorafenib and 19 to placebo. Thirteen patients assigned to placebo switched to regorafenib after progression. Median follow-up was 27.2 months (95% confidence interval [CI]: 24.4-not reached). We observed a significant PFS benefit of regorafenib compared with placebo (adjusted HR = 0.33; 95% CI: 0.15-0.74; p = 0.0007 median PFS = 2.1 versus 1.1 months, respectively), and a large and nearly significant overall survival (OS) benefit despite the cross-over (adjusted HR = 0.49; 95% CI: 0.23-1.06; p = 0.007; median OS = 17.8 versus 8.2 months). Before cross-over, the most common grade III or higher adverse events were lymphopenia (5 versus 1, respectively), diarrhoea (4 versus 0), dyspnoea (3 versus 1), skin toxicity (3 versus 0), arterial hypertension (2 versus 0), and increased transaminases (2 versus 0). Conclusion: The present study demonstrated a meaningful clinical anti-tumour activity with regorafenib in heavily pre-treated patients with non-adipocytic STS. (C) 2019 Elsevier Ltd. All rights reserved.

引用

页码：45 / 55

页数：11