Phase I/II Study of Cediranib and Olaparib in Combination for Treatment of Recurrent Papillary-Serous Ovarian, Fallopian Tube, or Peritoneal Cancer or for Treatment of Recurrent Triple-Negative Breast Cancer

Platinum sensitive ovarian cancer

162 (90 ovarian; median 2 prior therapies)

Recurrence

Open-Label, Randomized

ORR, PFS, OS, evaluated per RECIST

Exploratory: gBRCA1/2

Ola+Ced vs Ola:

ORR: 79.6 vs 47.8% (p=0.002)
PFS: 16.5 vs 8.2 months, HR: 0.50 (0.30-0.83, p=0.006)
OS: 44.2 vs 33.3 months, HR: 0.64 (0.36-1.11, p=0.11)

Exploratory analysis gBRCA status:
Ola+Ced vs Ola:
gBRCA WT  or UNK (n=43):
ORR: 76 vs 32% (p=0.006); PFS: 23.7 vs 5.7 months, HR: 0.31 (p=0.0013); OS: 37.8 vs 23.0 months, HR: 0.44 (p=0.047)
gBRCA MUT (n=47):
ORR: 83 vs 63% (p=0.19); PFS: 16.4 vs 16.5 months, HR: 0.76 (p=0.42); OS: 44.2 vs 40.1 months, HR: 0.86 (p=0.70)

Ola+Ced vs Ola:
Serious AE: none
Grade 3-4 AE: any (70 vs 11%), hypertension (41 vs 0%), fatigue (27 vs 11%), diarrhea (25 vs 0%)

Improved PFS and OS for combination therapy in patients with germline BRCA WT or unknown BRCA status

Liu J et al. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol (2014) 15(11):1207-14
http://www.ncbi.nlm.nih.gov/pubmed/25218906

Liu et al. Overall survival and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer. Annal Oncol (2019) 30(4):551-557
https://www.ncbi.nlm.nih.gov/pubmed/30753272