TY - JOUR
T1 - REGOSARC
T2 - Regorafenib versus placebo in doxorubicin-refractory soft-tissue sarcoma—A quality-adjusted time without symptoms of progression or toxicity analysis
AU - Berry, Vincent
AU - Basson, Laurent
AU - Bogart, Emilie
AU - Mir, Olivier
AU - Blay, Jean Yves
AU - Italiano, Antoine
AU - Bertucci, François
AU - Chevreau, Christine
AU - Clisant-Delaine, Stéphanie
AU - Liegl-Antzager, Bernadette
AU - Tresch-Bruneel, Emmanuelle
AU - Wallet, Jennifer
AU - Taieb, Sophie
AU - Decoupigny, Emilie
AU - Le Cesne, Axel
AU - Brodowicz, Thomas
AU - Penel, Nicolas
N1 - Publisher Copyright:
© 2017 American Cancer Society
PY - 2017/6/15
Y1 - 2017/6/15
N2 - 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 <.001). CONCLUSIONS: For patients with doxorubicin-pretreated soft-tissue sarcoma, regorafenib significantly improved quality-adjusted survival in comparison with a placebo. Cancer 2017;123:2294–2302.
AB - 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 <.001). CONCLUSIONS: For patients with doxorubicin-pretreated soft-tissue sarcoma, regorafenib significantly improved quality-adjusted survival in comparison with a placebo. Cancer 2017;123:2294–2302.
KW - metastatic soft-tissue sarcoma
KW - placebo
KW - quality-adjusted survival
KW - quality-adjusted time without symptoms of progression or toxicity (Q-TWiST)
KW - regorafenib
UR - http://www.scopus.com/inward/record.url?scp=85020268203&partnerID=8YFLogxK
U2 - 10.1002/cncr.30661
DO - 10.1002/cncr.30661
M3 - Article
C2 - 28295221
AN - SCOPUS:85020268203
SN - 0008-543X
VL - 123
SP - 2294
EP - 2302
JO - Cancer
JF - Cancer
IS - 12
ER -