TY - JOUR
T1 - A Single-Arm Phase II Trial of Sitravatinib in Advanced Well-Differentiated/Dedifferentiated Liposarcoma
AU - Ingham, Matthew
AU - Lee, Shing
AU - Van Tine, Brian A.
AU - Choy, Edwin
AU - Oza, Jay
AU - Doshi, Sahil
AU - Ge, Liner
AU - Oppelt, Peter
AU - Cote, Gregory
AU - Corgiat, Brian
AU - Sender, Naomi
AU - Sta Ana, Sarah
AU - Panchalingam, Lavan
AU - Petricoin, Emmanuel
AU - Schwartz, Gary K.
N1 - Publisher Copyright:
©2022 American Association for Cancer Research.
PY - 2023/3/14
Y1 - 2023/3/14
N2 - PURPOSE: To evaluate sitravatinib, an inhibitor of multiple receptor tyrosine kinases (RTK), for the treatment of well-differentiated/dedifferentiated liposarcoma (WD/DD LPS). PATIENTS AND METHODS: This multicenter, open-label, Phase II trial enrolled patients with advanced WD/DD LPS who had received at least one prior systemic regimen and had progression within 12 weeks of enrollment. Patients received sitravatinib 150 mg (later amended to 120 mg) orally daily. A Simon two-stage design was used to evaluate for an improvement in the primary endpoint, progression-free rate at 12 weeks (PFR12), from 20% to 40%. Secondary endpoints included antitumor activity and safety. A subset of patients underwent paired biopsies analyzed using reverse-phase protein array. RESULTS: Twenty-nine patients enrolled. Median age was 62 years and 31% had received 3 or more prior lines. Most patients (93%) had DDLPS or mixed WD/DD LPS. Overall, 12 of 29 patients (41%) were alive and progression-free at 12 weeks and the study met the primary endpoint. There were no confirmed responses. Median progression-free survival was 11.7 weeks [95% confidence interval (CI): 5.9-35.9] and median overall survival was 31.7 weeks (95% CI: 18.1-90.1). The most common treatment-related adverse events were diarrhea (59%), hypertension (52%), hoarseness (41%), mucositis (31%), and nausea (31%). Baseline expression of phospho-RTKs was not significantly different between patients with and without clinical benefit from sitravatinib, but the number of samples was small. CONCLUSIONS: Sitravatinib provided a PFR12 of 41% and meaningful disease control in a subset of patients with advanced, progressive WD/DD LPS.
AB - PURPOSE: To evaluate sitravatinib, an inhibitor of multiple receptor tyrosine kinases (RTK), for the treatment of well-differentiated/dedifferentiated liposarcoma (WD/DD LPS). PATIENTS AND METHODS: This multicenter, open-label, Phase II trial enrolled patients with advanced WD/DD LPS who had received at least one prior systemic regimen and had progression within 12 weeks of enrollment. Patients received sitravatinib 150 mg (later amended to 120 mg) orally daily. A Simon two-stage design was used to evaluate for an improvement in the primary endpoint, progression-free rate at 12 weeks (PFR12), from 20% to 40%. Secondary endpoints included antitumor activity and safety. A subset of patients underwent paired biopsies analyzed using reverse-phase protein array. RESULTS: Twenty-nine patients enrolled. Median age was 62 years and 31% had received 3 or more prior lines. Most patients (93%) had DDLPS or mixed WD/DD LPS. Overall, 12 of 29 patients (41%) were alive and progression-free at 12 weeks and the study met the primary endpoint. There were no confirmed responses. Median progression-free survival was 11.7 weeks [95% confidence interval (CI): 5.9-35.9] and median overall survival was 31.7 weeks (95% CI: 18.1-90.1). The most common treatment-related adverse events were diarrhea (59%), hypertension (52%), hoarseness (41%), mucositis (31%), and nausea (31%). Baseline expression of phospho-RTKs was not significantly different between patients with and without clinical benefit from sitravatinib, but the number of samples was small. CONCLUSIONS: Sitravatinib provided a PFR12 of 41% and meaningful disease control in a subset of patients with advanced, progressive WD/DD LPS.
UR - http://www.scopus.com/inward/record.url?scp=85150226179&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-22-3351
DO - 10.1158/1078-0432.CCR-22-3351
M3 - Article
C2 - 36548343
AN - SCOPUS:85150226179
SN - 1078-0432
VL - 29
SP - 1031
EP - 1039
JO - Clinical cancer research : an official journal of the American Association for Cancer Research
JF - Clinical cancer research : an official journal of the American Association for Cancer Research
IS - 6
ER -