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)

Trial ID # NCT00753545; Study 19
Phase II
Drug Class DNA Damage Repair Pathway Inhibitors: PARP
Drug Name Olaparib
Alternate Drug Names AZD2281, Lynparza
Drugs in Trial Olaparib
Eligible Participant

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

Patients Enrolled

265

Therapy Setting

Maintenance

Study Design

Double Blind, Randomized

Endpoints

PFS, OS, evaluated per RECIST

Biomarkers

Exploratory: BRCA1/2

Efficacy

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)

Clinically Significant Adverse Events

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

Conclusion

Improved PFS and OS with olaparib maintenance

Reference

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