Pazopanib Maintenance Therapy in East Asian Women With Advanced Epithelial Ovarian Cancer: Results From AGO-OVAR16 and an East Asian Study.

Abstract

OBJECTIVE:

The recent phase 3 trial AGO-OVAR16 demonstrated that pazopanib maintenance improved median progression-free survival in patients with ovarian cancer whose disease did not progress during first-line treatment. However, this improvement was not seen in the subset of East Asian patients. The current analysis evaluated the efficacy and safety of pazopanib maintenance in East Asian patients from AGO-OVAR16 and a separate East Asian study.

MATERIALS AND METHODS:

East Asian patients from AGO-OVAR16 (n = 209) and the East Asian study (N = 145) were randomized 1:1 to receive pazopanib 800 mg/d or placebo for up to 24 months. The primary end point for each study was progression-free survival by RECIST (Response Evaluation Criteria in Solid Tumors) based on investigator assessment. Clinical and genetics data were analyzed separately by study or pooled according to separate predetermined statistical plans.

RESULTS:

Pazopanib maintenance had a detrimental effect on median progression-free survival versus placebo in East Asian patients from the combined studies (n = 354; 17.9 vs 21.5 months; hazard ratio, 1.114; 95% confidence interval, 0.818-1.518; P = 0.4928). Pazopanib maintenance showed a disadvantage in overall survival in East Asian patients from AGO-OVAR16 versus placebo (hazard ratio, 1.706; 95% confidence interval, 1.010-2.883; P = 0.0465); overall survival analysis was not performed in the East Asian study because of insufficient event numbers. Pazopanib-treated patients had a significantly higher incidence of grade 3 or higher hypertension (27%) and neutropenia (13%) versus placebo.

CONCLUSIONS:

The treatment effect of maintenance pazopanib in East Asian patients seemed to differ from that in non-Asian patients. In study-specific and pooled analyses, none of the potential factors analyzed could satisfactorily explain the different efficacy results of pazopanib in East Asian patients.

• Authors: Jae-Weon Kim, Sven Mahner, Ling-Ying Wu, Tadahiro Shoji, Byoung-Gie Kim, Jian-Qing Zhu, Tadao Takano, Sang-Yoon Park, Bei-Hua Kong, Qiang Wu, Kung-Liahng Wang, Hextan Ys Ngan, Ji-Hong Liu, Li-Hui Wei, Ionel Mitrica, Pingkuan Zhang, Rocco Crescenzo, Qiong Wang, Charles J Cox, Philipp Harter, Andreas du Bois
• Journal: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society (Int J Gynecol Cancer) Vol. 28 Issue 1 Pg. 2-10 (01 2018) ISSN: 1525-1438 [Electronic] England
• PMID: 26588236 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)

Chemical References

• Indazoles
• Protein Kinase Inhibitors
• Pyrimidines
• Sulfonamides
• pazopanib
• FLT1 protein, human
• Vascular Endothelial Growth Factor Receptor-1

Topics

• Adult
• Aged
• Aged, 80 and over
• Asian People
• Carcinoma, Ovarian Epithelial
• Disease-Free Survival
• Double-Blind Method
• Asia, Eastern
• Female
• Humans
• Indazoles
• Middle Aged
• Neoplasms, Glandular and Epithelial (drug therapy, genetics, pathology)
• Ovarian Neoplasms (drug therapy, genetics, pathology)
• Protein Kinase Inhibitors (administration & dosage, adverse effects)
• Pyrimidines (administration & dosage, adverse effects)
• Sulfonamides (administration & dosage, adverse effects)
• Vascular Endothelial Growth Factor Receptor-1 (antagonists & inhibitors)
• Young Adult