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Ann Oncol. 2019 Feb 7. doi: 10.1093/annonc/mdz018. [Epub ahead of print]

Overall survival and updated progression-free survival outcomes in a randomized phase 2 study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer.

Author information

1
Department of Medical Oncology, Division of Gynecologic Oncology, Dana-Farber Cancer Institute, Boston, USA.
2
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, USA.
3
Department of Medical Oncology, Massachusetts General Hospital, Boston, USA.
4
Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, USA.
5
Department of Internal Medicine, University of Pittsburgh Hillman Cancer Center, Pittsburgh, USA.
6
Section of Hematology/Oncology, University of Chicago, Chicago, USA.
7
Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, USA.
8
Division of Hematology/Oncology, Beth-Israel Deaconess Medical Center, Boston, USA.
9
Department of Oncology, Fort Wayne Medical Oncology and Hematology, Fort Wayne, USA.
10
Division of Gynecologic Oncology, NorthShore University HealthSystem, Evanston Hospital, Evanston, USA.
11
Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, USA.

Abstract

Background:

Olaparib is a poly(ADP-ribose) polymerase (PARP) inhibitor and cediranib is an oral anti-angiogenic. In the primary analysis of this phase 2 study, combination cediranib/olaparib improved progression-free survival (PFS) compared to olaparib alone in relapsed platinum-sensitive ovarian cancer. This updated analysis was conducted to characterize overall survival (OS) and update PFS outcomes.

Patients and Methods:

90 patients were enrolled to this randomized, open-label, phase 2 study between October 2011 and June 2013 across nine United States-based academic centers. Data cut-off was December 21, 2016, with a median follow-up of 46 months (mos). Participants had relapsed platinum-sensitive ovarian cancer of high-grade serous or endometrioid histology or had a deleterious germline BRCA1/2 mutation (gBRCAm). Participants were randomized to receive olaparib capsules 400mg twice daily or cediranib 30mg daily and olaparib capsules 200mg twice daily until disease progression.

Results:

In this updated analysis, median PFS remained significantly longer with cediranib/olaparib compared to olaparib alone (16.5 vs. 8.2 mos, HR 0.50; p = 0.007). Subset analyses within stratum defined by BRCA status demonstrated statistically significant improvement in PFS (23.7 vs 5.7 mos, p = 0.002) and OS (37.8 vs 23.0 mos, p = 0.047) in gBRCA wild-type/unknown patients, although OS was not statistically different in the overall study population (44.2 vs. 33.3 mos, HR 0.64; p = 0.11). PFS and OS appeared similar between the two arms in gBRCAm patients. The most common grade 3/4 adverse events with cediranib/olaparib remained fatigue, diarrhea, and hypertension.

Conclusions:

Combination cediranib/olaparib significantly extends PFS compared to olaparib alone in relapsed platinum-sensitive ovarian cancer. Subset analyses suggest this margin of benefit is driven by PFS prolongation in patients without gBRCAm. OS was also significantly increased by the cediranib/olaparib combination in this subset of patients. Additional studies of this combination are ongoing and should incorporate analyses based upon BRCA status.

PMID:
30753272
DOI:
10.1093/annonc/mdz018

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