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Eur J Cancer. 2020 Feb;126:45-55. doi: 10.1016/j.ejca.2019.12.001. Epub 2020 Jan 6.

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.

Author information

1
Medical Oncology Department, Centre Oscar Lambret, Lille and Lille University Hospital, Lille University, Lille, France. Electronic address: n-penel@o-lambret.fr.
2
Medical Oncology Department, Gustave Roussy, Villejuif, France.
3
Clinical Research and Innovation Department, Centre Oscar Lambret, Lille, France.
4
Medical Oncology Department, Centre Léon Bérard, Lyon, France.
5
Medical Oncology Department, Institut Bergonié, Bordeaux, France.
6
Medical Oncology Department, CH La Timone, Marseille, France.
7
Medical Oncology Department, Centre François Baclesse, Caen, France.
8
Medical Oncology Department, René Gauducheau, Saint-Herblain, France.
9
Medical Oncology Department, Institut Paoli-Calmette, Marseille, France.
10
Medical Oncology Department, Centre Antoine Lacassagne, Nice, France.
11
Medical Oncology Department, Hopital Saint-Jacques, Besançon, France.
12
Medical Oncology Department, Institut Universitaire de Cancérologie de Toulouse, Oncopôle, Toulouse, France.
13
Medical University Vienna - General Hospital, Vienna, Austria.
14
Labeled Datacenter, Caen, France.
15
Radiology Department, Centre Oscar Lambret, Lille, France.
16
Clinical Research and Innovation Department, Centre Oscar Lambret, Lille, France; Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.

Abstract

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 α = 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.

KEYWORDS:

Angiogenesis; Pazopanib; Randomized phase II trial; Regorafenib; Soft tissue sarcoma

PMID:
31918233
DOI:
10.1016/j.ejca.2019.12.001

Conflict of interest statement

Conflict of interest statement N.P. and J.Y.B. received research funding from Bayer HealthCare SA. A.L.C. declares personal fees from Novartis, PharmaMar, Pfizer, Lilly and Ariad, outside the submitted work. O.M. reports personal fees from Roche, Pfizer, Novartis, Bayer, Amgen, Astra-Zeneca and BMS, outside the submitted work. All other authors declare that they have no conflicts of interest.

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