Phase II Randomised, Double Blind, Multicentre Study to Assess the Efficacy of AZD2281 in the Treatment of Patients With Platinum Sensitive Relapsed Serous Ovarian Cancer Following Treatment With Two or More Platinum Containing Regimens (Study 19)

Platinum sensitive recurrence and CR or PR in most recent platinum-based therapy, ≥ 2 platinum-based regimens

265

Maintenance

Double Blind, Randomized

PFS, OS, evaluated per RECIST

Exploratory: BRCA1/2

Ola maint vs Placebo (investigator review):

PFS: 8.4 vs 4.8 months, HR: 0.35 (0.25-0.49, p<0.001)
OS: 29.8 vs 27.8 months, HR: 0.73 (0.55-0.96, p=0.025, 77% maturity)

Exploratory analysis BRCA status:
BRCA WT: (n=118)
PFS: 7.4 vs 5.5 months, HR: 0.54 (0.34-0.85, p=0.0075)
OS: 24.5 vs 26.6 months, HR: 0.83 (0.55-1.24, p=0.37, 84% maturity)
BRCA MUT: (n=136)
PFS: 11.2 vs 4.3 months, HR: 0.18 (0.11-0.31, p<0.00001)
OS: 34.9 vs 30.2 months, HR: 0.62 (0.41-0.94, p=0.025, 70% maturity)

Ola maint vs Placebo (BICR):
PFS: HR: 0.39 (0.27-0.55, p=0<0.001)

Ola maint vs Placebo:
Serious AE: any (22 vs 9%)
Grade 3-4 AE: anemia (6 vs 1%), fatigue (8 vs 3%)

Improved PFS and OS with olaparib maintenance

Ledermann J et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. NEJM (2012) 366:1382-92
http://www.ncbi.nlm.nih.gov/pubmed/22452356

Ledermann J et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol (2014) 15(8):852-61
http://www.ncbi.nlm.nih.gov/pubmed/24882434

Ledermann J et al. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol (2016) 17(11): 1579-89
http://www.ncbi.nlm.nih.gov/pubmed/27617661