Cancer Treatment Today

Pazopanib is an oral, multikinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -1/-2/-3, platelet-derived growth factor receptor (PDGFR) -/-, and c-Kit. Preclinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment. There re several recent studies for ovarian cancer.

As far as treatment, adding pazopanib (Votrient, GlaxoSmithKline) to the standard treatment regimen increased progression-free survival in women with advanced ovarian cancer. Dr. Friedlander performed a single agent study that obtained overall response rate of 18% in patients with measurable disease at baseline. The most common adverse events leading to discontinuation of study drug were grade 3 ALT (8%) and AST (8%) elevation. Only 1 grade 4 toxicity (peripheral edema) was reported. Clearly more research needs to be done before this drug can be routinely employed.

There are two studies of it with cyclophosphamide. Dinckic concluded that Pazopanib 600mg daily p.o. and metronomic cyclophosphamide 50mg daily p.o. is a feasible regimen for patients with recurrent platinum-resistant EOC and showed promising activity in this previously treated patient population. Another supportive study was updated in 2020 by Gulia et al.

1du Bois A, Floquet A, Kim J-W, et al. (2014) Incorporation of pazopanib in maintenance therapy of ovarian cancer. J Clin Oncol 32:33743382.

Randomized, double-blind, phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC): Results of an international Intergroup trial (AGO-OVAR16). J Clin Oncol 31, 2013 (suppl; abstr LBA5503)

Friedlander, M. at al, A Phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer (Article) .Gynecologic Oncology, Volume 119, Issue 1, October 2010, Pages 32-37Gulia S, Ghosh J, Bajpai J, et al. Pazopanib and oral cyclophosphamide in women with platinum-resistant or -refractory epithelial ovarian cancer [published online March 31, 2020]. JCO Global Oncology. doi: 10.1200/JGO.19.00331

Pignata S, Lorusso D, Scambia G, et al. Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): a randomised, open-label phase 2 trial. Lancet Oncol. 2015;16(5):561-568. doi: 10.10165/S1470-2045(15)70115

Richardson DL, Sill MW, Coleman RL, et al. Paclitaxel with and without pazopanib for persistent or recurrent ovarian cancer: a randomized clinical trial. JAMA Oncol. 2018;4(2):196-202. doi: 10.1001/jamaoncol.2017.4218