REGOSARC: Regorafenib versus placebo in doxorubicin‐refractory soft‐tissue sarcoma—A quality‐adjusted time without symptoms of progression or toxicity analysis

• Published in: Cancer 2017-06, Vol.123 (12), p.2294-2302
• Main Authors: Berry, Vincent, Basson, Laurent, Bogart, Emilie, Mir, Olivier, Blay, Jean‐Yves, Italiano, Antoine, Bertucci, François, Chevreau, Christine, Clisant‐Delaine, Stéphanie, Liegl‐Antzager, Bernadette, Tresch‐Bruneel, Emmanuelle, Wallet, Jennifer, Taieb, Sophie, Decoupigny, Emilie, Cesne, Axel, Brodowicz, Thomas, Penel, Nicolas
• Format: Article
• Language: English
• Subjects: Aged; Alopecia - chemically induced; Anorexia - chemically induced; Antineoplastic Agents - therapeutic use; Asthenia - chemically induced; Cancer; Diarrhea - chemically induced; Double-Blind Method; Doxorubicin; Fecal Incontinence - chemically induced; Female; Hand-Foot Syndrome - etiology; Hospitalization; Humans; Hypertension - chemically induced; Inhibitor drugs; Leiomyosarcoma - drug therapy; Life Sciences; Liposarcoma - drug therapy; Male; metastatic soft‐tissue sarcoma; Middle Aged; Mucositis - chemically induced; Oncology; Original; Patients; Phenylurea Compounds - therapeutic use; placebo; Proportional Hazards Models; Pyridines - therapeutic use; Quality; Quality of Life; quality‐adjusted survival; quality‐adjusted time without symptoms of progression or toxicity (Q‐TWiST); regorafenib; Sarcoma; Sarcoma - drug therapy; Sarcoma, Synovial - drug therapy; Sensitivity analysis; Severity of Illness Index; Stability analysis; Survival; Toxicity; Treatment Outcome
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.30661

BACKGROUND In a placebo‐controlled, randomized phase 2 trial (ClinicalTrials.gov identifier NCT01900743), regorafenib improved progression‐free survival (PFS) for patients with doxorubicin‐pretreated advanced nonadipocytic sarcoma. A quality‐adjusted time without symptoms of progression or toxicity (Q‐TWiST) post hoc exploratory analysis was applied to provide an integrated measure of its clinical benefit. METHODS In the base‐case analysis, each patient's overall survival (OS) was partitioned into 3 mutually exclusive health states: the time with a grade 3 or 4 adverse event (TOX), the time without symptoms of disease or grade 3 or 4 toxicity from treatment, and the time after tumor progression or relapse. The time spent in each state was weighted with a health‐state utility associated with that state and was summed to calculate the Q‐TWiST. The stability of the base‐case analysis was explored with several sensitivity analyses. RESULTS In nonadipocytic sarcoma, the PFS was (4.0 months [2.6‐5.5 months] with regorafenib vs 1.0 month [0.9‐1.8 months] with a placebo; hazard ratio, 0.36 [0.25‐0.53]; P < .0001); the OS was 13.4 months (8.6‐17.3 months) with regorafenib and 9.0 months (6.8‐12.5 months) with a placebo (hazard ratio, 0.67 [0.44‐1.02]). With the classic definition of TOX (including all grade 3 and 4 clinical adverse events), the Q‐TWiSTs were 8.0 months (7.0‐9.0 months) with regorafenib and 5.7 months (4.9‐6.4 months) with a placebo (P