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

Trial ID # NCT01116648
Phase II
Drug Class DNA Damage Repair Pathway Inhibitors:PARP
Drug Name Olaparib
Alternate Drug Names AZD2281, Lynparza
Drugs in Trial Cediranib, Olaparib
Eligible Participant

Platinum-sensitive, recurrent ovarian cancer

Patients Enrolled

162 (90 ovarian; median 2 prior therapies)

Therapy Setting

Recurrence

Study Design

Open-Label, Randomized

Endpoints

ORR, PFS, OS, evaluated per RECIST

Biomarkers

Exploratory: gBRCA1/2

Efficacy

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=0.007)
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: 0.32 (p=0.002); OS: 37.8 vs 23.0 months, HR: 0.48 (p=0.074)
gBRCA MUT (n=47):
ORR: 83 vs 63% (p=0.19); PFS: 16.4 vs 16.5 months, HR: 0.75 (p=0.42); OS: 44.2 vs 40.1 months, HR: 0.79 (p=0.55)

Clinically Significant Adverse Events

Ola+Ced vs Ola:
Serious AE: none
Grade 3-4 AE: any (70 vs 11%), hypertension (41 vs 0%), fatigue (27 vs 11%), diarrhea (23 vs 0%)

Conclusion

Improved PFS and ORR for combination therapy, particularly in patients with germline BRCA WT or unknown BRCA status

Reference

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 results from a randomized phase 2 trial comparing the combination of olaparib and cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer. J Clin Oncol (2017) 35 (suppl; abstr 5535)
http://abstracts.asco.org/199/AbstView_199_188186.html