Olaparib, durvalumab, and cyclophosphamide, and a prognostic blood signature in platinum-sensitive ovarian cancer: the randomized phase 2 SOLACE2 trial
SOLACE2 (ACTRN12618000686202) investigates whether 12-weeks of olaparib, or cyclophosphamide-olaparib priming, improves subsequent durvalumab-olaparib progression-free survival (PFS), and is superior to olaparib monotherapy without any priming, in platinum-sensitive recurrent ovarian cancer (n = 114). We also evaluate the utility of CUP-CC assay, an immune signature of C-C chemokine receptor type 4 up-regulation, chemokines, and cytokines. Priming with olaparib, or cyclophosphamide-olaparib, followed by durvalumab-olaparib, are both associated with longer PFS compared to olaparib monotherapy, but do not reach the pre-specified primary endpoint of 36-week trial threshold (PFS36). PFS36 rates are 47.4% (95% CI, 31.0-62.1; olaparib priming then olaparib-durvalumab), 48.7% (32.5-63.2; olaparib-cyclophosphamide then olaparib-durvalumab) and 35.1% (20.4-50.3; olaparib monotherapy). PFS is significantly longer for the homologous recombination deficient (N = 71) as compared to the proficient (HRP) (N = 29) subgroups (Hazard Ratio (HR) 0.55, 0.35-0.87). CUP-CC+ subgroup (N = 58) has a significantly longer PFS (HR 0.31, 0.19-0.49) than CUP-CC- (N = 46). Future studies should investigate whether CUP-CC has the potential to personalize poly (ADP-ribose) polymerase inhibitor therapies for patients who are BRCA wild-type, including HRP patients.
Authors
- Matthew J. Wakefield (ORCID: https://orcid.org/0000-0001-6624-4698)
- Sally E. Baron-Hay (ORCID: https://orcid.org/0000-0002-9748-1458)
- Cassandra J. Vandenberg (ORCID: https://orcid.org/0000-0002-8891-8873)
- Emily Cassar (ORCID: https://orcid.org/0009-0000-3214-4613)
- Janine Lombard (ORCID: https://orcid.org/0000-0002-9551-0542)
- Hina Amer (ORCID: https://orcid.org/0000-0002-6359-4956)
- Katherine E. Francis (ORCID: https://orcid.org/0000-0002-8555-0161)
- Michael Leonard Friedlander (ORCID: https://orcid.org/0000-0003-3090-795X)
- Cyril Deceneux (ORCID: https://orcid.org/0000-0002-8074-045X)
- Claire M. Davies (ORCID: https://orcid.org/0000-0001-8651-0914)
- Rachel O’Connell (ORCID: https://orcid.org/0000-0001-5990-8142)
- Catherine Shannon (ORCID: https://orcid.org/0000-0002-2078-2869)
- Yoland Antill (ORCID: https://orcid.org/0000-0002-6366-5523)
- Michael Quinn (ORCID: https://orcid.org/0000-0003-0694-3870)
- Sandy Simon (ORCID: https://orcid.org/0009-0005-1274-2575)
- Kristy Shield‐Artin (ORCID: https://orcid.org/0000-0002-3969-9846)
- Ksenija Nesic (ORCID: https://orcid.org/0000-0001-9972-9819)
- Mutsa Madondo (ORCID: https://orcid.org/0000-0002-0958-6314)
- Momodou Cox (ORCID: https://orcid.org/0000-0002-2610-5017)
- Anthony T. Papenfuss (ORCID: https://orcid.org/0000-0002-1102-8506)
- U. G. I. U. Kariyawasam (ORCID: https://orcid.org/0000-0003-3540-8607)
- Philip Beale (ORCID: https://orcid.org/0000-0003-3628-4597)
- Justin Bedő (ORCID: https://orcid.org/0000-0001-5704-0212)
- Nirashaa Bound (ORCID: https://orcid.org/0009-0006-5847-0277)
- Magdalena Plebanski (ORCID: https://orcid.org/0000-0001-6889-3667)
- Chee Khoon Lee (ORCID: https://orcid.org/0000-0003-2955-9820)
- Apriliana E. R. Kartikasari (ORCID: https://orcid.org/0000-0002-8115-4866)
- Yeh Chen Lee (ORCID: https://orcid.org/0000-0003-2009-8263)
- Danka Sinikovic Zebic (ORCID: https://orcid.org/0000-0001-9370-3722)
- Katrina Diamante
- Clare L. Scott (ORCID: https://orcid.org/0000-0002-3689-5956)
- Georgia Goodchild (ORCID: https://orcid.org/0000-0001-9845-9570)
- Andrew Jarratt
- Sudarshan Selva‐Nayagam (ORCID: https://orcid.org/0000-0001-7823-6679)
- Anneliese Linaker
Institutions
- The University of Sydney (AU)
- Mater Health Services (AU)
- Royal Adelaide Hospital (AU)
- Royal Women's Hospital (AU)
- The University of Melbourne (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Royal Hospital for Women (AU)
- Royal North Shore Hospital (AU)
- Peter MacCallum Cancer Centre (AU)
- Monash Medical Centre (AU)
- UNSW Sydney (AU)
- Chris O’Brien Lifehouse (AU)
- Peninsula Health (AU)
- St George Hospital (AU)
- Australia New Zealand Gynaecological Oncology Group (AU)
- National Health and Medical Research Council (AU)
- Monash University (AU)
- RMIT University (AU)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-05
- DOI
- https://doi.org/10.1038/s41467-025-64130-6
- Citations
- 2
- Primary Topic
- PARP inhibition in cancer therapy
- Type
- article
- Field-Weighted Citation Impact
- 2.09
Funders
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Gilead Sciences
- Genomic Health
- Clovis Oncology
- Australian Government
- BeiGene
- Australian Cancer Research Foundation
- University of Sydney
- RMIT University
- Eisai
- Sierra Oncology
- Genentech
- National Health and Medical Research Council
- Cancer Council Victoria
- Daiichi Sankyo Europe