TY - JOUR
T1 - A phase II study of cabozantinib and androgen ablation in patients with hormone-naïve metastatic prostate cancer
AU - Corn, Paul G.
AU - Zhang, Miao
AU - Nogueras-Gonzalez, Graciela M.
AU - Xiao, Lianchun
AU - Zurita, Amado J.
AU - Subudhi, Sumit K.
AU - Tu, Shi-Ming
AU - Aparicio, Ana M.
AU - Coarfa, Cristian
AU - Rajapakshe, Kimal
AU - Huang, Shixia
AU - Navone, Nora M.
AU - Lin, Sue Hwa
AU - Wang, Guocan
AU - Ramachandran, Sumankalai
AU - Titus, Mark A.
AU - Panaretakis, Theocharis
AU - Gallick, Gary E
AU - Efstathiou, Eleni
AU - Troncoso, Patricia
AU - Logothetis, Christopher
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research Inc.. All rights reserved.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - Purpose: Cabozantinib, an oral inhibitor of c-MET/VEGFR2 signaling, improved progression-free survival (mPFS) but not overall survival (OS) in metastatic castrate-resistant prostate cancer. We evaluated cabozantinib plus androgen deprivation therapy (ADT) in hormone-naïve metastatic prostate cancer (HNMPCa). Patients and Methods: Patients received ADT plus cabozantinib starting at 60 mg daily. The primary endpoint was castrate-resistant PFS by radiographic criteria, clinical progression, or receipt of additional therapy. Secondary endpoints included OS, safety, radiographic responses, and biomarker modulation. Results: Sixty-two patients received treatment. With a median follow-up of 31.2 months, the mPFS was 16.1 months (95% CI, 14.6-22.7 months), and mOS was not reached. Reductions in PSA ≽ 90%, bone-specific alkaline phosphatase ≽ 50%, and urine N-telopeptides ≽ 50% occurred in 83%, 87%, and 86% of evaluable patients, respectively. Responses in bone scan and measurable disease were observed in 81% of and 90% of evaluable patients, respectively. Most common grade 3 adverse events were hypertension (19%), diarrhea (6%), and thromboembolic events (6%), and dose reductions occurred in 85% of patients. Analysis of baseline cytokine and angiogenic factors (CAFs) revealed that higher plasma concentrations of Lumican, CXCL5, CD25, and CD30 were associated with shorter PFS as was high tumor expression of pFGFR1. Conclusions: Cabozantinib plus ADT has promising clinical activity in HNMPCa. CAF profiles and tissue markers suggest candidate prognostic and predictive markers of cabozantinib benefit and provide insights for rational therapy combinations.
AB - Purpose: Cabozantinib, an oral inhibitor of c-MET/VEGFR2 signaling, improved progression-free survival (mPFS) but not overall survival (OS) in metastatic castrate-resistant prostate cancer. We evaluated cabozantinib plus androgen deprivation therapy (ADT) in hormone-naïve metastatic prostate cancer (HNMPCa). Patients and Methods: Patients received ADT plus cabozantinib starting at 60 mg daily. The primary endpoint was castrate-resistant PFS by radiographic criteria, clinical progression, or receipt of additional therapy. Secondary endpoints included OS, safety, radiographic responses, and biomarker modulation. Results: Sixty-two patients received treatment. With a median follow-up of 31.2 months, the mPFS was 16.1 months (95% CI, 14.6-22.7 months), and mOS was not reached. Reductions in PSA ≽ 90%, bone-specific alkaline phosphatase ≽ 50%, and urine N-telopeptides ≽ 50% occurred in 83%, 87%, and 86% of evaluable patients, respectively. Responses in bone scan and measurable disease were observed in 81% of and 90% of evaluable patients, respectively. Most common grade 3 adverse events were hypertension (19%), diarrhea (6%), and thromboembolic events (6%), and dose reductions occurred in 85% of patients. Analysis of baseline cytokine and angiogenic factors (CAFs) revealed that higher plasma concentrations of Lumican, CXCL5, CD25, and CD30 were associated with shorter PFS as was high tumor expression of pFGFR1. Conclusions: Cabozantinib plus ADT has promising clinical activity in HNMPCa. CAF profiles and tissue markers suggest candidate prognostic and predictive markers of cabozantinib benefit and provide insights for rational therapy combinations.
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U2 - 10.1158/1078-0432.CCR-19-2389
DO - 10.1158/1078-0432.CCR-19-2389
M3 - Article
C2 - 31941830
AN - SCOPUS:85081137646
SN - 1078-0432
VL - 26
SP - 990
EP - 999
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 5
ER -