A randomized phase II evaluation of weekly gemcitabine plus pazopanib versus weekly gemcitabine alone in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma.
Gynecol Oncol
; 157(3): 585-592, 2020 06.
Article
in En
| MEDLINE
| ID: mdl-32247603
ABSTRACT
OBJECTIVE:
Angiogenesis inhibition is a valuable strategy for ovarian cancer (EOC). Pazopanib (paz) is a potent small molecular inhibitor of VEGF-1, -2, -3, PDGFR, c-kit, and has activity as a single agent in ovarian cancer. We designed a trial to assess the benefit of adding paz to gemcitabine (gem) in patients with recurrent EOC.METHODS:
An open-label, randomized, multi-site, phase 2 trial was conducted (NCT01610206) including patients with platinum resistant or sensitive disease, ≤ 3 prior lines of chemotherapy, and measurable/evaluable disease. Patients were randomly assigned to weekly gem 1000 mg/m2 on days 1 and 8 of a 21 day cycle, with or without paz 800 mg QD, stratified by platinum sensitivity and number of prior lines (1 vs 2 or 3). The primary endpoint was PFS.RESULTS:
148 patients were enrolled 2012-2017. Median age was 63 years (30-82); 60% were platinum resistant; median surveillance was 13 months (0.4-54 months). Median PFS was 5.3 (95% CI, 4.2-5.8) vs 2.9 months (95% CI, 2.1-4.1) in the gem arm. The PFS effect was most pronounced in the platinum resistant group (5.32 vs 2.33 months Tarone-Ware p < 0.001). There was no difference in OS. Overall RR (PR 20% vs 11%, Chi-squre p = 0.02) and DCR (80% vs 60%, Chi-square p < 0.001) were higher in the combination. High grade AEs in the combination arm included ≥ Grade 3 hypertension (15%), neutropenia (35%), and thrombocytopenia (12%).CONCLUSIONS:
The addition of paz to gem enhanced anti-tumor activity; those with platinum-resistant disease derived the most benefit from combination therapy, even in the setting of receiving prior bevacizumab.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peritoneal Neoplasms
/
Pyrimidines
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Sulfonamides
/
Deoxycytidine
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Fallopian Tube Neoplasms
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Carcinoma, Ovarian Epithelial
Type of study:
Clinical_trials
Limits:
Adult
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Aged
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Aged80
/
Female
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Humans
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Middle aged
Language:
En
Journal:
Gynecol Oncol
Year:
2020
Document type:
Article