Blood‐based biomarkers in patients with recurrent, persistent, or metastatic endometrial cancer treated with olaparib and cediranib: Results from NRG‐GY012
Abstract Background The NRG‐GY012 phase 2 trial evaluated olaparib, cediranib, and the combination in 120 patients with recurrent, persistent, or metastatic endometrial cancer (EC). Predictive and prognostic associations between blood‐based biomarkers and clinical outcomes were assessed. Methods Plasma samples collected at baseline, cycle 4 day 1, and disease progression were analyzed for circulating protein biomarkers (Angiome). The primary analysis evaluated the predictive impact of IL‐6 on progression‐free survival (PFS) and overall survival (OS). The predictive and prognostic impact of all other markers on PFS and OS were also evaluated. Results Ninety‐six baseline plasma samples were included in this analysis. Results from GOG‐218 identified IL‐6 was predictive of clinical benefit using a threshold of 2.9 pg/mL. Although the 2.9 pg/mL cut point did not validate in GY012, IL‐6 associated with OS using the median level of 4.2 pg/mL as the cut point. Although patients with >4.2 pg/mL IL‐6 had worse prognosis, higher IL‐6 levels were associated with longer OS benefit in the cediranib arms ( p intx = .085). In secondary analyses, osteopontin (OPN) and placental growth factor (PlGF) potentially predicted benefit. Patients with higher OPN levels had shorter OS in the olaparib arm, whereas patients with lower OPN had longer OS in the cediranib arms ( p intx = .035). Patients with higher PlGF benefited more from cediranib (PFS, p intx = .030; OS, p intx = .024). Multiple prognostic markers were also identified. Conclusions IL‐6 may be predictive of outcome; OPN and PlGF represent novel potential predictive biomarkers, in EC patients receiving anti‐angiogenic therapy. Further evaluation is warranted.
Authors
- Matthew A. Powell (ORCID: https://orcid.org/0000-0002-9001-3862)
- Tara Castellano (ORCID: https://orcid.org/0000-0002-6131-2927)
- Floor Jenniskens Backes (ORCID: https://orcid.org/0000-0002-9225-6913)
- David Bender (ORCID: https://orcid.org/0000-0002-9192-510X)
- Laura L. Holman (ORCID: https://orcid.org/0000-0003-1580-5381)
- Jesús González Bosquet (ORCID: https://orcid.org/0000-0002-2079-4528)
- Colleen Lee Rivard (ORCID: https://orcid.org/0000-0002-1922-080X)
- Yingmiao Liu (ORCID: https://orcid.org/0000-0003-3516-5844)
- Dan S. Veljovich (ORCID: https://orcid.org/0000-0001-9264-808X)
- Andrew B. Nixon (ORCID: https://orcid.org/0000-0003-3971-2964)
- Helen J MacKay (ORCID: https://orcid.org/0000-0001-6220-1789)
- Danielle M. Enserro (ORCID: https://orcid.org/0000-0003-2132-9967)
- Mark Gregory Cadungog (ORCID: https://orcid.org/0009-0008-6027-2872)
- John William Moroney (ORCID: https://orcid.org/0000-0003-4387-5387)
- Mark D. Starr (ORCID: https://orcid.org/0009-0003-9664-6235)
- Angeles Alvarez Secord (ORCID: https://orcid.org/0000-0003-0946-7662)
- Julia Fehniger (ORCID: https://orcid.org/0000-0003-1773-7060)
- J. Chris Brady
- B.J. Rimel (ORCID: https://orcid.org/0000-0003-4808-3805)
Institutions
- Roswell Park Comprehensive Cancer Center (US)
- University of Minnesota (US)
- Sunnybrook Health Science Centre (CA)
- University of Washington (US)
- Washington University in St. Louis (US)
- Legacy Good Samaritan Medical Center (US)
- University of Iowa Hospitals and Clinics (US)
- University of Chicago (US)
- Fred Hutch Cancer Center (US)
- Christiana Hospital (US)
- Duke Medical Center (US)
- St. Luke’s Boise Medical Center (US)
- Oklahoma State University Oklahoma City (US)
- Odette Cancer Centre (CA)
- University of Oklahoma Health Sciences Center (US)
- The Ohio State University (US)
- Louisiana State University Health Sciences Center New Orleans (US)
Publication Details
- Journal
- Cancer
- Published
- 2026-10-14
- DOI
- https://doi.org/10.1002/cncr.70649
- Primary Topic
- Endometrial and Cervical Cancer Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Cancer Institute