MedicalResearch.com Interview with:
Debra Richardson, MD, FACOG, FACS
Associate Professor, Section of Gynecologic Oncology,
Oklahoma TSET Phase I Program
Stephensen Cancer Center
The University of Oklahoma
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Ovarian cancer is the leading cause of gynecologic cancer deaths. Pazopanib is an oral multitarget tyrosine kinase inhibitor of VEGF receptors 1, 2, and 3; platelet-derived growth factor (PDGF) receptors α and β and c-KIT. Weekly paclitaxel is an active agent for recurrent ovarian cancer.
This was a national, randomized, double-blind, placebo controlled phase 2b trial of weekly paclitaxel with or without pazopanib for the treatment of recurrent ovarian cancer. The primary objective was to estimate the progression-free survival (PFS) hazard ratio (HR) of the combination of weekly paclitaxel (80mg/m2 D1, 8, 15 every 28 days) and pazopanib (800mg PO daily) compared with weekly paclitaxel and placebo in women with persistent or recurrent ovarian cancer. 106 women were enrolled. There was no difference in median PFS, overall survival (OS), or proportion responding. Severe hypertension was more common on the pazopanib plus paclitaxel arm. More patients discontinued treatment on the paclitaxel arm for disease progression, and more on the pazopanib plus paclitaxel arm for adverse events. Patients with VEGFA CC genotype may be more resistant to weekly paclitaxel than those with the AC or AA genotype.
MedicalResearch.com: What should readers take away from your report?
Response: There is no statistical difference in proportion responding, PFS, or OS for women with recurrent ovarian cancer treated with weekly paclitaxel alone versus weekly paclitaxel with pazopanib. The combination arm was more toxic.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: More work should be done to determine if the VEGFA CC genotype is more resistant to treatment with weekly paclitaxel. If that finding is confirmed- it could potentially help avoid ineffective chemotherapy in those women.
MedicalResearch.com: Is there anything else you would like to add?
Response: The findings of our trial- GOG 186J- differ from MITO-11 (Weekly Paclitaxel With or Without Pazopanib in Platinum-Resistant or Refractory Ovarian Cancer by Pignata et al). The MITO-11 study demonstrated a 2.86-month improvement in PFS for women on the combination arm, which was statistically significant. However, there are important differences between MITO-11 and our trial. MITO-11 was not placebo controlled, only platinum-resistant and -refractory patients were included, and patients with a history of treatment with bevacizumab were excluded. Results from this current study (GOG 186J) do not support further investigation of this combination in this patient population at these doses and schedule.
Reference for Pignata trial: Pignata S, Lorusso D, Scambia G, et al; MITO 11 investigators. 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.
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Richardson DL, Sill MW, Coleman RL, et al. Paclitaxel with and without pazopanib in persistent or recurrent ovarian cancer: a randomized clinical trial. JAMA Oncol. Published Online: December 14, 2017. doi:10.1001/jamaoncol.2017.4218
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